10 ms·

Thanks, HN: You helped discover a disease and save lives

1483 points by mattmight 12y ago

(There's a shout-out to HN in the article.) Two years ago, HN was the first to pick up on a post I wrote about my son's preliminary diagnosis via experimental exome sequencing: https://news.ycombinator.com/item?id=4038113 Two years ago, he was the only known NGLY1 deficient patient in the world. By spreading the story, we've found 16 cases worldwide. We've organized. We've found preliminary treatments. Clinical trials are in the pipeline. In some cases, we've saved the lives of previously undiagnosed patients. And, these children's cells are turning into gold mines for the basic science of glycobiology. From the bottom of my heart and on behalf of the entire small but optimistic NGLY1 community, Thank you.

mattmight 12y ago
(There's a shout-out to HN in the article.) Two years ago, HN was the first to pick up on a post I wrote about my son's preliminary diagnosis via experimental exome sequencing: https://news.ycombinator.com/item?id=4038113 https://news.ycombinator.com/item?id=4038113 Two years ago, he was the only known NGLY1 deficient patient in the world. By spreading the story, we've found 16 cases worldwide. We've organized. We've found preliminary treatments. Clinical trials are in the pipeline. In some cases, we've saved the lives of previously undiagnosed patients. And, these children's cells are turning into gold mines for the basic science of glycobiology. From the bottom of my heart and on behalf of the entire small but optimistic NGLY1 community, Thank you.
- nowarninglabel 12y ago
  I remember the story, it was very powerful. Thank you for not giving up and making the world a better place by continually working hard to find answers.
- sadfaceunread 12y ago
  Very impressive management of the situation. This story is pretty incredible and really exciting for the ability of researchers at different institutions to somewhat effectively collaborate.
- aidos 12y ago
  Thanks so much for posting the update. I remember the story well (my daughter was about 6 months old at the time so it really resonated) and I've occasionally stopped and wondered how things had progressed since then. It's inspiring to hear how you've all dealt with it as a family. And amazing to see that against all odds you've made some real progress that has (and will forever) affect people's lives in a meaningful way.
  - mattmight 12y ago
    Thanks for the kind words. If you had told me when my son was born that we'd have to discover a disease as just the first (small) step toward saving him, we would have crumbled. We weren't ready for what had to be done. But, parenting a child with a rare disease changes you in ways you can't imagine. I've seen it again and again it in the thousands of rare disease parents we've met over the years. A slow-motion grieving process gives way to a visceral, evolutionary response: whatever it takes, save the child. You can drive a truckload of bad news right over these parents. They get up, dust themselves off and keep walking. You stop thinking about the future. Entirely. You start thinking about what you can do today and right now. You force yourself to take the first small step. Then another, and another. Day to day, it never seems like you're making progress. But, I've seen rare disease parents end up achieving the impossible by just focusing on one small step toward the impossible at at time. I realize we've come far, but I know we have a long way to go. So, on to the next step.
    - knicholes 12y ago
      This is so awesome. I've kept from reading it again to avoid letting my coworkers note my emotion.
    - smoyer 12y ago
      This is so very true ... the endurance that it takes to have a disabled child is something I never knew was in my character. After choosing a career that was well-known for death-marches, that's the closest analogy I can offer (this crowd). Unlike a death-march, you never grow to hate the process: sometimes you grit your teeth just to take that next step, but your heart demands you continue. After reading your story, I realize I walked a much easier path - my son was born with trisomy-21 (Down Syndrome) and it was easily diagnosed (though not so easily accepted by us parents). It turned out he had several more genetic disorders, but as each was identified, it was (more easily) dealt with. I can't even imagine going through his first five years gathering questions but receiving no answers. We have two children older than our disabled son, and when people asked me what I wanted them to be when they grew up, I was always quick to answer "happy". You've given so much (both for Betrand and the others you've gathered together) that I don't want to take anything away from your amazing journey. I do want to give you what I can here - a simple blessing. May God bless you and your family so that you always find strength in him and in each other, and may your eyes be quick to see those small joys and victories so many people miss in their hectic lives. Thanks so much for sharing both the original story and the follow-up! EDIT: There's so much to say! I'll keep it brief though. I should have noted that growing up in a household with a disabled child has had a profound impact on my other three children. My older two are adults now (and Sam just turned 18) but from a young age they had empathy and sympathy that far exceeded what most adults feel. It's actually shaped their character in a tremendously good way. [1] Exceptional Lives - http://www.blurb.com/b/651459-exceptional-lives http://www.blurb.com/b/651459-exceptional-lives [2] Your Special Chef (Cookbook) - http://www.blurb.com/search/site_search?search=your+special+chef http://www.blurb.com/search/site_search?search=your+special+... [3] Your Special Chef (Website) - http://www.yourspecialchef.com http://www.yourspecialchef.com [4] My favorite molecular geneticist - http://annamoyer.com/assets/resumesum2013_moyer.jpg http://annamoyer.com/assets/resumesum2013_moyer.jpg
- TeMPOraL 12y ago
  Thank you for this update. I remember your story well and I'm happy that you've made so much progress to cure your son. It is people like you, and the hard work you do, that drives the progress of mankind. Like in your Ph.D. post, the boundary of all medical knowledge gave way, and you've created a dent. A dent that will improve and save many lives. Thank you for your contribution, and best of luck on the way to curing your son!
- amputect 12y ago
  This is a really heartening story both because it's objectively amazing and, to me, for personal reasons. My wife suffers from an unknown congenital myopathy. She, and by extension I, are actually VERY fortunate. It's a very mild expression of that class of disease, so it's not a death sentence, but it's a life sentence. She can walk unaided and climb stairs (slowly, with effort), but she'll never run, among other things. She has very weak muscles in her extremities, a very high resting heartrate, breathing problems, and she basically can't gain muscle mass. She has been working with doctors on both coasts to try to nail down a diagnosis, so that we can think about having children (we need to know what, exactly, to screen for). So far, we have had many promising diagnoses, all of which have been negative. We might be looking at a new disease, and the information in the article about genetic sequencing for new diseases lines up with what her doctor at the NIH has been working on (they just recently collected genetic material from her close relatives). Thank you for sharing a success story on the new disease front, and thank you for your work to turn your personal tragedy into a force for good in the world. You're the best kind of people.
  - mattmight 12y ago
    I wish you and your wife much luck. If the docs at NIH come back with a pile of variants of unknown clinical significance, get in touch with me. I'll help you find patient #2.
    - sarciszewski 12y ago
      "I'll help you find patient #2." Awesome. I would give a million upvotes if I could. Your dedication to helping others is worthy of deep respect. :)
    - amputect 12y ago
      Thank you so much, this means a lot to both of us.
    - jipiboily 12y ago
      Humanity at its best! <3
  - 12y ago
- zeidrich 12y ago
  I think it's incredible what we can do with a medium like the Internet. It is a shame that so much intellectual capacity gets tied up in academic glory-seeking, and it's refreshing to see that the power of the connectivity of the Internet can let a lay person make stronger connections than a secretive academic. Hopefully this and other stories like this will promote more active communication and sharing of ideas over silenced and competition for publication credit.
- 2muchcoffeeman 12y ago
  So, technology wise, what have you learned from this? Your internet presence helped you find an audience. How do we help people who don't have that but still have access to the internet? At what point do people with chronic and untreated illness realise they may have something very rare?
  - mattmight 12y ago
    There's no doubt that my technical blog helped do this the first time. But, I firmly believed that this could be repeated without an established presence. And, it has been repeated. After I co-authored an article with a fellow parent describing how social media + sequencing could discover diseases, a family with an undiagnosed child reached out to me. They had been exome sequenced, but they were left with two de novo mutations of unknown clinical significance. It wasn't clear if either was the cause of their child's symptoms. I gave them advice on how to structure a site with the highest likelihood of finding another patient. They created this on their own: http://milosjourney.com/ http://milosjourney.com/ Within 29 days, they found a second patient with a de novo mutation in the same gene (KDM1A). Just looking at the kids made it obvious they had the same disorder. And, so KDM1A has become the second disease discovered by social media + sequencing. The heartening aspect is that this family didn't have a prior social media presence at all. I recommended that they buy Google AdWords on the names of the candidate genes of unknown clinical significance they were given, but even that wasn't necessary. So, I'd recommend that anyone going through a diagnostic odyssey and start blogging everything -- medical terms, lay terms, doctors names, symptoms, medications, treatment attempts, etc. These are all the kinds of things that fellow sufferers are likely to type into Google.
    - Tomte 12y ago
      Recently I was googling for NGLY1 references on German language web sites and found some very short thread in a child healthcare forum (or something similar) where some parent described their child, some other guy said it sounded a bit like your case and linked to your site, and the OP replied that it sounded similar indeed and they'd be in touch. I don't know if that was really one of the cases, but your web site sure has impact.
- hirenj 12y ago
  Hi Matt - It's inspiring to read more about your story, and that you've been making some progress with Hud Freeze, with some potential results from an inhibitor? Hud Freeze came to visit our lab (he's on the steering committee of our centre) shortly after we met. For sure, there's no one else in the world that is better suited to figure this out. I figure I should chime in here with some info about glycobiology and disease. The issue of rare diseases highlights an issue with disease discovery, in that techniques such as GWAS don't really have the power to identify these rare diseases, and that our current pipelines to find these diseases won't really work. Searching for these disease associations is a bit like looking for a needle in a series of small independent haystacks that may or may not share hay. Since our gut feeling with glycobiology is that we are talking about mostly rare diseases or subtle phenotypes, our goal is to use more of an integrated approach (taking data from many -omics strategies) to try and pinpoint subsystems that are affected by disease. Concretely, we're trying to expand outreach with our knowledge of mutations in glycosylation related genes, and we should be submitting a manuscript next week on the start of our work trying to find some of these relevant rarer mutations. It'll be coupled with some web pages (right after I find some time to generate them), that make it a bit easier for non-glycobiologists to get information out about these genes. The larger and more comprehensive this resource is, the better. The ubiquity of sequencing data that is coming out now is making a huge difference in our field. One challenge, as mentioned below, is getting centralised access to all this data. If anyone knows of a great bit of software where I can feed in data from various exome sequencing populations, that has a REST api for retrieving variants (and ideally amino acid changes) I would be interested to hear of this, since it will save me time writing it myself. As an aside - there was an article that floated off the front page here about blood types, and why we have them, and is another example of the relevance of glycobiology, and the difficulty in understanding mutations. Basically for the blood type gene, you can have single variation causing a single amino acid change pretty much all over the gene, and they all very subtly (or not so subtly) alter the activity of the gene. To pick out which one of the variations is deleterious is not trivial. In the field of glycobiology, there's still a lot of work to do, but I think we're making some progress, and I hope we can actually unlock some secrets, and give help to people soon.
  - davecap1 12y ago
- PauloManrique 12y ago
  Your story bought me to tears, as I started to remember my baby that died in 2010. He was premature and I don't think it's related to the case of your son. I wish all the best for you, hope that your son manage to grow up and live his life, in the best possible way. All my prayers for your son and the others fighting on that.
- cybernoodles 12y ago
  This really is a testament to how badly technology is needed in the medical field to document and cross reference these sorts of cases. It's hard to think of such an important industry being so disconnected in such a highly connected era.
- linux_devil 12y ago
  Wish all these patients healthy life ahead , and Matt I can't describe your efforts in words , reading that article I feel that you and your wife are best parents in the world ! Good luck .
djb_hackernews 12y ago
Wow, I remember this story. I asked a question about your sons development if the therapy went well and you responded, and I find myself pondering what the outcome is every now and then. Just wanted to say all the best and keep us updated.
- mattmight 12y ago
  Thanks for the kind words and your original comments! I'll certainly post another update when we reach the next critical milestone in this disorder. We're making rapid progress in understanding these kids at a cellular level. I'm very hopeful. I'm also hopeful that the (apparently advantageous) immunological aspects of NGLY1 deficiency will have broader benefit to mankind.
  - mylons 12y ago
    I'm glad someone else is being helped by DNA sequencing. It's such a promising new field, and why I do it
    - mattmight 12y ago
      Thank you!
  - Zikes 12y ago
    That must be an incredible feeling, knowing you and your family may play a part in a potentially world-changing discovery. I hope things continue to improve for you and everyone involved in this endeavour, and I look forward to more updates.
revelation 12y ago
Can someone knowledgable explain why we can't manipulate viruses to patch our genome? I don't know why that doesn't work, I just know enough to realize it would be an enormously useful thing.
- dm2 12y ago
  http://en.wikipedia.org/wiki/Retrovirus#Gene_therapy http://en.wikipedia.org/wiki/Retrovirus#Gene_therapy "modern medicine" isn't perfect, it's good and getting better every day, but we have a long way to go. Plus, we don't know for sure what modifying our DNA does. It might affect certain things, but it might also have unknown consequences. There is a ton of trial and error in science, and you don't want to have too many errors in your body, else it leads to cancer and other horrible things. Lots of mice have given their lives to ensure that we and our children live awesome healthy lives. Thank you lab-rats (and other animals), you have suffered for our benefit (though you didn't have much of a choice). Also, it's really really difficult and really tiny, https://www.youtube.com/watch?v=TfYf_rPWUdY https://www.youtube.com/watch?v=TfYf_rPWUdY but there are several teams working on it and many other approaches.
- mylons 12y ago
  to sum it you, it's very hard to target the specific location in the genome you want to correct/overwrite. A virus will just insert it's payload where ever it wants, which almost certainly will cause unintended consequences in your genome
- DennisP 12y ago
  We can and it's a very active area of research, called gene therapy. An early attempt gave a kid cancer, so people are still pretty cautious about it, but things are much improved now, and patients with a variety of diseases have been successfully treated. http://en.wikipedia.org/wiki/Gene_therapy http://en.wikipedia.org/wiki/Gene_therapy
  - dekhn 12y ago
    Another attempt caused a massive immune reaction. That said, the amount of furor over a few deaths in gene therapy trials seems to be irrational: far worse things happen in cancer treatment all the time. I really wanted gene therapy to be available 20 years ago and even went to grad school to learn how to make it work. It was strongly deemphasized at my school in a preference for classic small-molecule protein inhibitor therapy. Gene therapy is truly non-trivial. It took me several decades of studies in genomics and protein functional informatics to appreciate how subtle and complex the problem is. I'm hopeful that we can make technology that enables routine personalized gene therapy a common form of therapy, but it is truly not an easy problem. Causing cancer and immune response is only the first set of easily observed (fatal) side effects.
micro_cam 12y ago
What a success story! I was surprised to see that the second child wasn't sequenced earlier. A family of four study or even a study that includes grandparents is significantly more powerful then a trio study. Even if only one individual displays the phenotypes it allows more variants to be eliminated and potentially allows an increased ability to distinguish sequencing errors from rare variants and new mutations. It also lets you more precisely identify recombination sites: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037280/figure/F2/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037280/figure/F...
jobu 12y ago
Amazing how gene sequencing has really started to pay off. A member of my family was recently diagnosed with two mutations of the MTHFR gene. This comes after years of trying different horrible depression medications, thyroid drugs, and hormone pills that often made things worse. While some of the treatments are still guesses, it's so much better to finally be treating the root cause and not just guessing at how to suppress symptoms.
hkiely 12y ago
Regardless if we can or can't manipulate our DNA with approaches such as gene therapy, we first must get therapeutics to patients with rare and orphan conditions in an adequate amount of time. Many patients wait on the the hurdles set in place by the FDA who think they are protecting patients safety. However, with a quickly progressing illness and no treatment, often the patient will die without the drug that is being withheld. The YouTube Video Shows Dr. Bill Gahl of the NIH Undiagnosed Diseases Program speaking at a TED event. https://www.youtube.com/watch?v=aMMBmc_pQVA https://www.youtube.com/watch?v=aMMBmc_pQVA
- mattmight 12y ago
  We're up against this right now for NGLY1. There's a compound in trials right now that has shown tremendous promise in my son's cells in the lab and in the cells of other NGLY1 patients. But, we can't get permission to give it to him, and setting up a clinical trial for NGLY1 keeps getting ever-more delayed because of concern over the FDA. Meanwhile, our children suffer. I'm very worried that some are going to die before this clinical trial gets underway. (Incidentally, Bertrand and I got to meet Bill Gahl while admitted at the NIH for a week-long research protocol that will systematically study all known NGLY1 patients.)
  - kanzure 12y ago
    > But, we can't get permission to give it to him Have you considered making it yourself without permission? Suppose for a moment that there exists a sequence of tests that you feel would adequately prove the safety or efficacy of a homebrew solution. Obviously, at least some sequence of tests must exist that seems pretty okay since the clinical trials have somewhat trustworthy results. The actual cost of enzyme production (actually, I haven't studied the solution that would be going through clinical trails in detail) can be much lower than the $X billion that Big Pharma claims. For example, $50k can get you a basic antibody garage biology operation going, without cutting corners absolutely everywhere. I know a handful of people with equipment and expertise eager to prove this. After all, your original mission wasn't "fighting regulatory hurdles". Successful FDA clinical trials are nice, but not if everyone dies while busy waiting to raise $100M to resubmit FDA forms. edit: Looks like you found a place to buy a batch for $250? Be safe.
fuzzythinker 12y ago
This snippet is the most interesting: > perhaps Bertrand was able to avoid infections because viruses got stuck after attaching themselves to his defective glycoproteins. Rosenzweig is quick to emphasize that until he can test other NGLY1 patients he won’t know if his hypothesis warrants further exploration. But if it bears out, he says, it could point to a way to treat acute infections ranging from influenza to Ebola hemorrhagic fever.
Mz 12y ago
Two over-the-counter supplements seemed to be helping, as well. The first was a highly concentrated cocoa extract. “It sounds like a scam, except there’s research showing that cocoa actually improves cells’ energy production,” Matt told me. The second was N-acetylcysteine, or NAC, an amino acid that helps produce a naturally occurring antioxidant. At the time of the original post, I asked a question. A PHD biologist kindly wrote me via email and answered some of my questions. I have a form of Cystic Fibrosis, as does my oldest son. It is a different homozygous recessive disorder. The biologist confirmed some of my inferences about how cell biology works and that this disorder likely had some things in common with CF. NAC is something known to also help CF patients. It makes me wonder what other treatments are being used and if the doctors have compared it at all to CF.
- mattmight 12y ago
  CF has popped up more than once when looking at treatments for NGLY1. In fact, the first ever treatment we tested in the lab was a read-through compound often used to treat some forms of CF: gentamycin. It didn't work for Bertrand, but it may still work for other NGLY1 patients. Phenotypically, there are some overlaps with NGLY1 and CF, so there may be commonalities in the underlying mechanisms of harm. I'll ask the NGLY1 researchers what they think about a CF-NGLY1 link.
  - Mz 12y ago
    Thank you for replying. My memory of the discussion is fuzzy, but I talked a bit for a couple of days with this biologist and then I wrote a long blog post with my thoughts. My recollection is that my conclusion was that due to the way that NGLY1 works, Bertrand should be deficient in a number of proteins that work as, among other things, cell channels, including but not limited to the CFTR, which is the one involved in CF. So it seems to me he should have some of the same issues, like specific deficiencies, high acidity, etc.
  - dnautics 12y ago
    I don't know if there's still an active cell line in the lab, but have they tested 1-deoxynojirimycin, or nojirimycin? Although they're glycosidase inhibitors, since this is a lysosomal storage disease, IIRC one copy of the NGLY gene is dead because of a nonsense mutation but the other has an uncharacterized, non-catalytic mutation. This one might be rescuable through a "chemical chaperoning" effect, ironically the proper treatment then is an inhibitor to the enzyme you're trying to save. Relevant research on a (beta-) glycosidase (but presumably the active site structure and thus the inhibitory mechanism of nojirimycin should be similar): http://www.pnas.org/content/99/24/15428.short http://www.pnas.org/content/99/24/15428.short Also I had a short discussion with Dr. Freeze about his results showing that flooding with mannose (not therapeutically viable) improves activity, mannose is a weak NGLY1 inhibitor. Also Mz: I was the biologist that responded to your query!
dangoldin 12y ago
Touching story. A reminder that for all the gadgets we get, the internet is really about connecting and helping people.
jopela 12y ago
Does anyone know if a website already exists that would help people with such rare genetic condition find each other? Not everyone is able to capitalize on being a popular blogger and it could help those people find help and support. This could also serve other kind of patients in dire situations such as: https://ca.news.yahoo.com/blogs/daily-brew/montreal-cancer-patient-rallies-against-limited-number-minority-173801245.html https://ca.news.yahoo.com/blogs/daily-brew/montreal-cancer-p...
- mattmight 12y ago
  There is no such web site. I've advised another family on how to repeat our success, and they managed to find a second patient by setting up a website for their child. Both kids had de novo mutations in KDM1A and could be mistaken for brothers. So, sequencing + social media has already discovered a second disease. After the success with Bertrand and NGLY1, the NIH reached out to me to see if there was a way that they could integrate social media into their Undiagnosed Disease Program. Unfortunately, the NIH can't (or won't) set up anything right now. There's an urgent need for this too: genome sequencing is going to unearth the raw data necessary to discover thousands of new genetic disorders like NGLY1 deficiency over the next decade. But, if that data stays isolated, those discoveries just won't happen. Kids won't get diagnosed. If only there were a site full of technically minded entrepreneurs that we could share this opportunity with...
  - refurb 12y ago
    Have you reached out to NORD (National Organization for Rare Diseases)? They don't have a website for connecting patients with rare diseases, but they are a pretty well run organization that help connect people the old fashion way.
  - eric_bullington 12y ago
    Hi Matt, I've been inspired to start setting up something myself. Long story why, but in short I've got kids of my own around Bertrand's age (also, my own son is named after famous scientist and thinker). They were born healthy, and can't imagine going through what you all have. Also, pre-software development, I did grad school in public health (lots of epi and biostat in a dept of inhl health) and briefly worked in health research. So I may be in a good position to help out. I'm in the process of setting up something using Flask right now and will soon (next few hours) open source it on Github and open it up for contributions. I can't absolutely guarantee that I'll be able to maintain it long-term, but I can certainly get a forum, site, and member registry database up and going and open sourced. Hopefully in such a way that it could be managed by a non-programmers (I realize you have such skills but you obviously have your plate full). Perhaps eventually it could bloom into a full registry of genetic data, pending resolution of privacy issues (maybe using something like dnasubway). I'd really love to team with an established designer(s) on this. I can hack up a UI, but would be best to team with a designer(s). I'd also love to team up with other devs who are interested. Would sociallyrare.org be an ok name for a social media hub for rare diseases? I went ahead and registered that name, but if you have any other suggestions/requests I'd love to hear them. Not sure if Socially Rare has the right ring to it.
Caldercho 12y ago
Such an inspiring story.
TeMPOraL 12y ago
Matt's struggle to find the cause and cure of his son's disease reminded me of a post I read sometime ago: http://lesswrong.com/lw/gvi/metamed_evidencebased_healthcare/ http://lesswrong.com/lw/gvi/metamed_evidencebased_healthcare... While probably not applicable in this case, I think many people struck with rare/weird diseases could find this service useful. MetaMed is basically a group of people who are really good at maths, know the newest medical technologies and procedures, and are willing to dig through and evaluate tons of medical papers and publications. I hope that this will help someone. I'm also interested if anyone on HN used this service and could tell how it worked out in their case.
timsally 12y ago
There are no words for this; an incredible story. My thoughts and prayers are with Bertrand and others with NGLY1 deficiency. It seems that while Professor and Christina Might were making a herculean effort to discover and fight NGLY1 deficiency, Professor Might was granted tenure (!) at the University of Utah and is considered a rising star (http://admin.utah.edu/academic_affairs_posts/rising-stars-at-the-u-2 http://admin.utah.edu/academic_affairs_posts/rising-stars-at...). I doubt anyone makes excuses for late homework in his class.
- mattmight 12y ago
  Thanks for the kind words and the nod, but I can assure you that there's still no shortages of excuses for late homework. Since this is HN, I'll share one thing that works: force your students to use git (or some version control) for assignments. Having an auditable history of effort makes it hard to lie. Except when it turns "the dog ate my homework" into "git rebase ate my homework."
  - ph0rque 12y ago
    "My dog forked my homework."
  - nitrogen 12y ago
    There's still the reflog for that excuse (e.g. .git/logs/refs/heads/master).
    - cookiecaper 12y ago
      Only sometimes. There are several actions that may purge items from and/or completely clear the reflog.
lilsunnybee 12y ago
> Patient-advocacy groups have been around for decades, but it’s extremely unusual for one or two families to single-handedly direct an international research agenda. It helps that both the Mights and the Wilseys have family money. (Matt Might’s father is the president and C.E.O. of Cable One, the cable-television division of the former Washington Post Company.) It's a really sad fact that economic inequality has a particularly dire effect on limiting access to quality healthcare and specialists for patients with rare diseases, no matter the severity. The diagnosis difficulties the Mights went through with their son are made much worse for parents who can't pay, even for much more common rare diseases. Hopefully someday our civilization can advance to the point where economic means matter much less than they do now for healthcare, where quality of life and opportunity to thrive is respected equally for every human, regardless of family money, or who gets the right to publish.
thinkcomp 12y ago
Question for Matt (or anyone who knows): What's the best or most cost-effective way to get an entire family sequenced? My younger brother has a rare disorder (diagnosed as autism and twelve other things that mean "we're not sure"), I don't have it, and we've wanted to get everyone sequenced for some time. Any thoughts would be appreciated.
- mattmight 12y ago
  You may want to check out LineaGen: http://www.lineagen.com/ http://www.lineagen.com/ It's cheaper than sequencing, and more importantly, they actually know what to do with the data once they have it. Getting your sequencing data is becoming cheaper and cheaper. Analyzing it is not.
deleted 12y ago
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gcb0 12y ago
all the best to the families. but this makes me furious at how research is done. everyone pays high tuition and dont think about it. just being glad their families can afford. but you (everyone here probably) is fostering this. expensive pedigree universities are the ones that create such toxic environment for open research. very similar to this was already documented in the "Lorenzo's oil" book/film. lets hope this time we learn the lesson. (yeah, high hopes of anyone here not favoring a Stanford student but anyway ...i have no idea how even start to break this vicious circle that promote inefficient research in that way... maybe killing patents will be the light?)
- QuantumChaos 12y ago
  I see two separate phenomena. The article describes researchers being rewarded for their publications, and therefore not sharing data with their competitors, who could create a publication with that data which the researcher who shared the data would get no credit for. You are describing people favoring graduates from top universities, which therefore charge higher tuition since their degrees are more valuable. I can't see any relationship between these two things, maybe you can clarify.
  - gcb0 12y ago
    the top universities are top universities because of what? the standard metric is number of published papers. So a university to on the top have to play by those rules. and we keeping regarding them as the top are by consequence valuing those rules. the hypocrisy has to end somewhere. We can't keep up voting those articles that point the problems with academic publishing while giving priority to hire from the institutions that maintain that status quo.
gravedave 12y ago
Wish there was a cliffnotes version of this long-winded article. Best of luck to the kid though.
Herdinger 12y ago
I suffer from a condition called visual snow. I realized about ten years ago that what I was expering wasn't normal. The condition was completly unknown at the time and I got multiple MRI's, my eyes and nervous system checked out from every angle and there was nothing abnormal. Talking with many people I know it turned out that this condition is surprisingly pretty common, though in a mild form. People told me they saw some form of constant noise too but dismissed it as normal. Your article got me to check the condition out again and it turns out there is new research from May identifing something wrong with the brain of people under the condition. It's nothing life threatening like you're story, but still it's something you have to learn to live with it's there 24/7 even when you close your eyes and can be imparing at night. http://www.eyeonvision.org/news/107-visual-snow-research-study.html http://www.eyeonvision.org/news/107-visual-snow-research-stu... http://en.wikipedia.org/wiki/Visual_snow http://en.wikipedia.org/wiki/Visual_snow Sadly I'm not in the US and there don't seem to be any research studies in Germany. Therefore I want to shout out if anyone on HN suffers from this condition, maybe hasn't even realized it because it manifests in mild form. You can all help the understanding of the condition.
- merlish 12y ago
  Oddly, I think I have this. I've tried to explain the vague faint multi-colour noise that overlays my vision that is especially noticeable at night to e.g. my parents before, and they didn't get it. I've always assumed it's normal and that I just failed to explain sufficiently. Reading the wiki article: > In addition to visual snow, many sufferers have other types of visual disturbances such as starbursts, increased afterimages, floaters, trails, and many others.[9] eh maybe; I have no frame of reference >Non-visual symptoms such as tinnitus, depersonalization-derealization, fatigue, speech difficulties and cognitive dysfunction (brain fog) are frequently encountered.[citation needed] Secondary psychiatric sequelae such as anxiety, panic attacks or depression may develop and necessitate appropriate treatment.[citation needed] Tinnitus: Yes, sometimes it flares up a bit for about half an hour before going away again. There's a background level of ringing in an even slightly quiet environment, but I'm not sure if it's just the blood rushing through my ears. I also like listening to music at a loud volume (I find it hard to enjoy music otherwise.) Depersonalization-derealization: Not sure. See 'depression' below. Fatigue: Yes, which I've associated with my depression Speech difficulties: I stutter and find it hard to remember names, but if I'm presenting something you would never realize either of these. Cognitive dysfunction: Quite possibly. If I'm in a more depressed mood, I can't think. Anxiety/panic attacks/depression: I was diagnosed with clinical depression a couple of years ago, when it got so bad I stopped caring about anything and went to a doctor. Headaches/migraines: It varies wildly, but I do get headaches quite badly on occasion. I put this down more to stress & depression.
ryansmurphy 12y ago
TOO MANY ONIONS..... Them dam feels
tuxguy 12y ago
Original article on Bertrand & how Matt Might investigated the cause of Bertrand's illness http://matt.might.net/articles/my-sons-killer/ http://matt.might.net/articles/my-sons-killer/
greenpinguin 12y ago
Amazing story!
xiaoma 12y ago
The actual title of the article is One of a kind.

1483 points by mattmight 12y ago

mattmight 12y ago

(There's a shout-out to HN in the article.) Two years ago, HN was the first to pick up on a post I wrote about my son's preliminary diagnosis via experimental exome sequencing: https://news.ycombinator.com/item?id=4038113 https://news.ycombinator.com/item?id=4038113 Two years ago, he was the only known NGLY1 deficient patient in the world. By spreading the story, we've found 16 cases worldwide. We've organized. We've found preliminary treatments. Clinical trials are in the pipeline. In some cases, we've saved the lives of previously undiagnosed patients. And, these children's cells are turning into gold mines for the basic science of glycobiology. From the bottom of my heart and on behalf of the entire small but optimistic NGLY1 community, Thank you.

nowarninglabel 12y ago
I remember the story, it was very powerful. Thank you for not giving up and making the world a better place by continually working hard to find answers.
sadfaceunread 12y ago
Very impressive management of the situation. This story is pretty incredible and really exciting for the ability of researchers at different institutions to somewhat effectively collaborate.
aidos 12y ago
Thanks so much for posting the update. I remember the story well (my daughter was about 6 months old at the time so it really resonated) and I've occasionally stopped and wondered how things had progressed since then. It's inspiring to hear how you've all dealt with it as a family. And amazing to see that against all odds you've made some real progress that has (and will forever) affect people's lives in a meaningful way.
- mattmight 12y ago
  Thanks for the kind words. If you had told me when my son was born that we'd have to discover a disease as just the first (small) step toward saving him, we would have crumbled. We weren't ready for what had to be done. But, parenting a child with a rare disease changes you in ways you can't imagine. I've seen it again and again it in the thousands of rare disease parents we've met over the years. A slow-motion grieving process gives way to a visceral, evolutionary response: whatever it takes, save the child. You can drive a truckload of bad news right over these parents. They get up, dust themselves off and keep walking. You stop thinking about the future. Entirely. You start thinking about what you can do today and right now. You force yourself to take the first small step. Then another, and another. Day to day, it never seems like you're making progress. But, I've seen rare disease parents end up achieving the impossible by just focusing on one small step toward the impossible at at time. I realize we've come far, but I know we have a long way to go. So, on to the next step.
  - knicholes 12y ago
    This is so awesome. I've kept from reading it again to avoid letting my coworkers note my emotion.
  - smoyer 12y ago
    This is so very true ... the endurance that it takes to have a disabled child is something I never knew was in my character. After choosing a career that was well-known for death-marches, that's the closest analogy I can offer (this crowd). Unlike a death-march, you never grow to hate the process: sometimes you grit your teeth just to take that next step, but your heart demands you continue. After reading your story, I realize I walked a much easier path - my son was born with trisomy-21 (Down Syndrome) and it was easily diagnosed (though not so easily accepted by us parents). It turned out he had several more genetic disorders, but as each was identified, it was (more easily) dealt with. I can't even imagine going through his first five years gathering questions but receiving no answers. We have two children older than our disabled son, and when people asked me what I wanted them to be when they grew up, I was always quick to answer "happy". You've given so much (both for Betrand and the others you've gathered together) that I don't want to take anything away from your amazing journey. I do want to give you what I can here - a simple blessing. May God bless you and your family so that you always find strength in him and in each other, and may your eyes be quick to see those small joys and victories so many people miss in their hectic lives. Thanks so much for sharing both the original story and the follow-up! EDIT: There's so much to say! I'll keep it brief though. I should have noted that growing up in a household with a disabled child has had a profound impact on my other three children. My older two are adults now (and Sam just turned 18) but from a young age they had empathy and sympathy that far exceeded what most adults feel. It's actually shaped their character in a tremendously good way. [1] Exceptional Lives - http://www.blurb.com/b/651459-exceptional-lives http://www.blurb.com/b/651459-exceptional-lives [2] Your Special Chef (Cookbook) - http://www.blurb.com/search/site_search?search=your+special+chef http://www.blurb.com/search/site_search?search=your+special+... [3] Your Special Chef (Website) - http://www.yourspecialchef.com http://www.yourspecialchef.com [4] My favorite molecular geneticist - http://annamoyer.com/assets/resumesum2013_moyer.jpg http://annamoyer.com/assets/resumesum2013_moyer.jpg
TeMPOraL 12y ago
Thank you for this update. I remember your story well and I'm happy that you've made so much progress to cure your son. It is people like you, and the hard work you do, that drives the progress of mankind. Like in your Ph.D. post, the boundary of all medical knowledge gave way, and you've created a dent. A dent that will improve and save many lives. Thank you for your contribution, and best of luck on the way to curing your son!
amputect 12y ago
This is a really heartening story both because it's objectively amazing and, to me, for personal reasons. My wife suffers from an unknown congenital myopathy. She, and by extension I, are actually VERY fortunate. It's a very mild expression of that class of disease, so it's not a death sentence, but it's a life sentence. She can walk unaided and climb stairs (slowly, with effort), but she'll never run, among other things. She has very weak muscles in her extremities, a very high resting heartrate, breathing problems, and she basically can't gain muscle mass. She has been working with doctors on both coasts to try to nail down a diagnosis, so that we can think about having children (we need to know what, exactly, to screen for). So far, we have had many promising diagnoses, all of which have been negative. We might be looking at a new disease, and the information in the article about genetic sequencing for new diseases lines up with what her doctor at the NIH has been working on (they just recently collected genetic material from her close relatives). Thank you for sharing a success story on the new disease front, and thank you for your work to turn your personal tragedy into a force for good in the world. You're the best kind of people.
- mattmight 12y ago
  I wish you and your wife much luck. If the docs at NIH come back with a pile of variants of unknown clinical significance, get in touch with me. I'll help you find patient #2.
  - sarciszewski 12y ago
    "I'll help you find patient #2." Awesome. I would give a million upvotes if I could. Your dedication to helping others is worthy of deep respect. :)
  - amputect 12y ago
    Thank you so much, this means a lot to both of us.
  - jipiboily 12y ago
    Humanity at its best! <3
- 12y ago
zeidrich 12y ago
I think it's incredible what we can do with a medium like the Internet. It is a shame that so much intellectual capacity gets tied up in academic glory-seeking, and it's refreshing to see that the power of the connectivity of the Internet can let a lay person make stronger connections than a secretive academic. Hopefully this and other stories like this will promote more active communication and sharing of ideas over silenced and competition for publication credit.
2muchcoffeeman 12y ago
So, technology wise, what have you learned from this? Your internet presence helped you find an audience. How do we help people who don't have that but still have access to the internet? At what point do people with chronic and untreated illness realise they may have something very rare?
- mattmight 12y ago
  There's no doubt that my technical blog helped do this the first time. But, I firmly believed that this could be repeated without an established presence. And, it has been repeated. After I co-authored an article with a fellow parent describing how social media + sequencing could discover diseases, a family with an undiagnosed child reached out to me. They had been exome sequenced, but they were left with two de novo mutations of unknown clinical significance. It wasn't clear if either was the cause of their child's symptoms. I gave them advice on how to structure a site with the highest likelihood of finding another patient. They created this on their own: http://milosjourney.com/ http://milosjourney.com/ Within 29 days, they found a second patient with a de novo mutation in the same gene (KDM1A). Just looking at the kids made it obvious they had the same disorder. And, so KDM1A has become the second disease discovered by social media + sequencing. The heartening aspect is that this family didn't have a prior social media presence at all. I recommended that they buy Google AdWords on the names of the candidate genes of unknown clinical significance they were given, but even that wasn't necessary. So, I'd recommend that anyone going through a diagnostic odyssey and start blogging everything -- medical terms, lay terms, doctors names, symptoms, medications, treatment attempts, etc. These are all the kinds of things that fellow sufferers are likely to type into Google.
  - Tomte 12y ago
    Recently I was googling for NGLY1 references on German language web sites and found some very short thread in a child healthcare forum (or something similar) where some parent described their child, some other guy said it sounded a bit like your case and linked to your site, and the OP replied that it sounded similar indeed and they'd be in touch. I don't know if that was really one of the cases, but your web site sure has impact.
hirenj 12y ago
Hi Matt - It's inspiring to read more about your story, and that you've been making some progress with Hud Freeze, with some potential results from an inhibitor? Hud Freeze came to visit our lab (he's on the steering committee of our centre) shortly after we met. For sure, there's no one else in the world that is better suited to figure this out. I figure I should chime in here with some info about glycobiology and disease. The issue of rare diseases highlights an issue with disease discovery, in that techniques such as GWAS don't really have the power to identify these rare diseases, and that our current pipelines to find these diseases won't really work. Searching for these disease associations is a bit like looking for a needle in a series of small independent haystacks that may or may not share hay. Since our gut feeling with glycobiology is that we are talking about mostly rare diseases or subtle phenotypes, our goal is to use more of an integrated approach (taking data from many -omics strategies) to try and pinpoint subsystems that are affected by disease. Concretely, we're trying to expand outreach with our knowledge of mutations in glycosylation related genes, and we should be submitting a manuscript next week on the start of our work trying to find some of these relevant rarer mutations. It'll be coupled with some web pages (right after I find some time to generate them), that make it a bit easier for non-glycobiologists to get information out about these genes. The larger and more comprehensive this resource is, the better. The ubiquity of sequencing data that is coming out now is making a huge difference in our field. One challenge, as mentioned below, is getting centralised access to all this data. If anyone knows of a great bit of software where I can feed in data from various exome sequencing populations, that has a REST api for retrieving variants (and ideally amino acid changes) I would be interested to hear of this, since it will save me time writing it myself. As an aside - there was an article that floated off the front page here about blood types, and why we have them, and is another example of the relevance of glycobiology, and the difficulty in understanding mutations. Basically for the blood type gene, you can have single variation causing a single amino acid change pretty much all over the gene, and they all very subtly (or not so subtly) alter the activity of the gene. To pick out which one of the variations is deleterious is not trivial. In the field of glycobiology, there's still a lot of work to do, but I think we're making some progress, and I hope we can actually unlock some secrets, and give help to people soon.
- davecap1 12y ago
PauloManrique 12y ago
Your story bought me to tears, as I started to remember my baby that died in 2010. He was premature and I don't think it's related to the case of your son. I wish all the best for you, hope that your son manage to grow up and live his life, in the best possible way. All my prayers for your son and the others fighting on that.
cybernoodles 12y ago
This really is a testament to how badly technology is needed in the medical field to document and cross reference these sorts of cases. It's hard to think of such an important industry being so disconnected in such a highly connected era.
linux_devil 12y ago
Wish all these patients healthy life ahead , and Matt I can't describe your efforts in words , reading that article I feel that you and your wife are best parents in the world ! Good luck .

djb_hackernews 12y ago

Wow, I remember this story. I asked a question about your sons development if the therapy went well and you responded, and I find myself pondering what the outcome is every now and then. Just wanted to say all the best and keep us updated.

mattmight 12y ago
Thanks for the kind words and your original comments! I'll certainly post another update when we reach the next critical milestone in this disorder. We're making rapid progress in understanding these kids at a cellular level. I'm very hopeful. I'm also hopeful that the (apparently advantageous) immunological aspects of NGLY1 deficiency will have broader benefit to mankind.
- mylons 12y ago
  I'm glad someone else is being helped by DNA sequencing. It's such a promising new field, and why I do it
  - mattmight 12y ago
    Thank you!
- Zikes 12y ago
  That must be an incredible feeling, knowing you and your family may play a part in a potentially world-changing discovery. I hope things continue to improve for you and everyone involved in this endeavour, and I look forward to more updates.

revelation 12y ago

Can someone knowledgable explain why we can't manipulate viruses to patch our genome? I don't know why that doesn't work, I just know enough to realize it would be an enormously useful thing.

dm2 12y ago
http://en.wikipedia.org/wiki/Retrovirus#Gene_therapy http://en.wikipedia.org/wiki/Retrovirus#Gene_therapy "modern medicine" isn't perfect, it's good and getting better every day, but we have a long way to go. Plus, we don't know for sure what modifying our DNA does. It might affect certain things, but it might also have unknown consequences. There is a ton of trial and error in science, and you don't want to have too many errors in your body, else it leads to cancer and other horrible things. Lots of mice have given their lives to ensure that we and our children live awesome healthy lives. Thank you lab-rats (and other animals), you have suffered for our benefit (though you didn't have much of a choice). Also, it's really really difficult and really tiny, https://www.youtube.com/watch?v=TfYf_rPWUdY https://www.youtube.com/watch?v=TfYf_rPWUdY but there are several teams working on it and many other approaches.
mylons 12y ago
to sum it you, it's very hard to target the specific location in the genome you want to correct/overwrite. A virus will just insert it's payload where ever it wants, which almost certainly will cause unintended consequences in your genome
DennisP 12y ago
We can and it's a very active area of research, called gene therapy. An early attempt gave a kid cancer, so people are still pretty cautious about it, but things are much improved now, and patients with a variety of diseases have been successfully treated. http://en.wikipedia.org/wiki/Gene_therapy http://en.wikipedia.org/wiki/Gene_therapy
- dekhn 12y ago
  Another attempt caused a massive immune reaction. That said, the amount of furor over a few deaths in gene therapy trials seems to be irrational: far worse things happen in cancer treatment all the time. I really wanted gene therapy to be available 20 years ago and even went to grad school to learn how to make it work. It was strongly deemphasized at my school in a preference for classic small-molecule protein inhibitor therapy. Gene therapy is truly non-trivial. It took me several decades of studies in genomics and protein functional informatics to appreciate how subtle and complex the problem is. I'm hopeful that we can make technology that enables routine personalized gene therapy a common form of therapy, but it is truly not an easy problem. Causing cancer and immune response is only the first set of easily observed (fatal) side effects.

micro_cam 12y ago

What a success story! I was surprised to see that the second child wasn't sequenced earlier. A family of four study or even a study that includes grandparents is significantly more powerful then a trio study. Even if only one individual displays the phenotypes it allows more variants to be eliminated and potentially allows an increased ability to distinguish sequencing errors from rare variants and new mutations. It also lets you more precisely identify recombination sites: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037280/figure/F2/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037280/figure/F...

jobu 12y ago

Amazing how gene sequencing has really started to pay off. A member of my family was recently diagnosed with two mutations of the MTHFR gene. This comes after years of trying different horrible depression medications, thyroid drugs, and hormone pills that often made things worse. While some of the treatments are still guesses, it's so much better to finally be treating the root cause and not just guessing at how to suppress symptoms.

hkiely 12y ago

Regardless if we can or can't manipulate our DNA with approaches such as gene therapy, we first must get therapeutics to patients with rare and orphan conditions in an adequate amount of time. Many patients wait on the the hurdles set in place by the FDA who think they are protecting patients safety. However, with a quickly progressing illness and no treatment, often the patient will die without the drug that is being withheld. The YouTube Video Shows Dr. Bill Gahl of the NIH Undiagnosed Diseases Program speaking at a TED event. https://www.youtube.com/watch?v=aMMBmc_pQVA https://www.youtube.com/watch?v=aMMBmc_pQVA

mattmight 12y ago
We're up against this right now for NGLY1. There's a compound in trials right now that has shown tremendous promise in my son's cells in the lab and in the cells of other NGLY1 patients. But, we can't get permission to give it to him, and setting up a clinical trial for NGLY1 keeps getting ever-more delayed because of concern over the FDA. Meanwhile, our children suffer. I'm very worried that some are going to die before this clinical trial gets underway. (Incidentally, Bertrand and I got to meet Bill Gahl while admitted at the NIH for a week-long research protocol that will systematically study all known NGLY1 patients.)
- kanzure 12y ago
  > But, we can't get permission to give it to him Have you considered making it yourself without permission? Suppose for a moment that there exists a sequence of tests that you feel would adequately prove the safety or efficacy of a homebrew solution. Obviously, at least some sequence of tests must exist that seems pretty okay since the clinical trials have somewhat trustworthy results. The actual cost of enzyme production (actually, I haven't studied the solution that would be going through clinical trails in detail) can be much lower than the $X billion that Big Pharma claims. For example, $50k can get you a basic antibody garage biology operation going, without cutting corners absolutely everywhere. I know a handful of people with equipment and expertise eager to prove this. After all, your original mission wasn't "fighting regulatory hurdles". Successful FDA clinical trials are nice, but not if everyone dies while busy waiting to raise $100M to resubmit FDA forms. edit: Looks like you found a place to buy a batch for $250? Be safe.

fuzzythinker 12y ago

This snippet is the most interesting: > perhaps Bertrand was able to avoid infections because viruses got stuck after attaching themselves to his defective glycoproteins. Rosenzweig is quick to emphasize that until he can test other NGLY1 patients he won’t know if his hypothesis warrants further exploration. But if it bears out, he says, it could point to a way to treat acute infections ranging from influenza to Ebola hemorrhagic fever.

Mz 12y ago

Two over-the-counter supplements seemed to be helping, as well. The first was a highly concentrated cocoa extract. “It sounds like a scam, except there’s research showing that cocoa actually improves cells’ energy production,” Matt told me. The second was N-acetylcysteine, or NAC, an amino acid that helps produce a naturally occurring antioxidant. At the time of the original post, I asked a question. A PHD biologist kindly wrote me via email and answered some of my questions. I have a form of Cystic Fibrosis, as does my oldest son. It is a different homozygous recessive disorder. The biologist confirmed some of my inferences about how cell biology works and that this disorder likely had some things in common with CF. NAC is something known to also help CF patients. It makes me wonder what other treatments are being used and if the doctors have compared it at all to CF.

mattmight 12y ago
CF has popped up more than once when looking at treatments for NGLY1. In fact, the first ever treatment we tested in the lab was a read-through compound often used to treat some forms of CF: gentamycin. It didn't work for Bertrand, but it may still work for other NGLY1 patients. Phenotypically, there are some overlaps with NGLY1 and CF, so there may be commonalities in the underlying mechanisms of harm. I'll ask the NGLY1 researchers what they think about a CF-NGLY1 link.
- Mz 12y ago
  Thank you for replying. My memory of the discussion is fuzzy, but I talked a bit for a couple of days with this biologist and then I wrote a long blog post with my thoughts. My recollection is that my conclusion was that due to the way that NGLY1 works, Bertrand should be deficient in a number of proteins that work as, among other things, cell channels, including but not limited to the CFTR, which is the one involved in CF. So it seems to me he should have some of the same issues, like specific deficiencies, high acidity, etc.
- dnautics 12y ago
  I don't know if there's still an active cell line in the lab, but have they tested 1-deoxynojirimycin, or nojirimycin? Although they're glycosidase inhibitors, since this is a lysosomal storage disease, IIRC one copy of the NGLY gene is dead because of a nonsense mutation but the other has an uncharacterized, non-catalytic mutation. This one might be rescuable through a "chemical chaperoning" effect, ironically the proper treatment then is an inhibitor to the enzyme you're trying to save. Relevant research on a (beta-) glycosidase (but presumably the active site structure and thus the inhibitory mechanism of nojirimycin should be similar): http://www.pnas.org/content/99/24/15428.short http://www.pnas.org/content/99/24/15428.short Also I had a short discussion with Dr. Freeze about his results showing that flooding with mannose (not therapeutically viable) improves activity, mannose is a weak NGLY1 inhibitor. Also Mz: I was the biologist that responded to your query!

dangoldin 12y ago

Touching story. A reminder that for all the gadgets we get, the internet is really about connecting and helping people.

jopela 12y ago

Does anyone know if a website already exists that would help people with such rare genetic condition find each other? Not everyone is able to capitalize on being a popular blogger and it could help those people find help and support. This could also serve other kind of patients in dire situations such as: https://ca.news.yahoo.com/blogs/daily-brew/montreal-cancer-patient-rallies-against-limited-number-minority-173801245.html https://ca.news.yahoo.com/blogs/daily-brew/montreal-cancer-p...

mattmight 12y ago
There is no such web site. I've advised another family on how to repeat our success, and they managed to find a second patient by setting up a website for their child. Both kids had de novo mutations in KDM1A and could be mistaken for brothers. So, sequencing + social media has already discovered a second disease. After the success with Bertrand and NGLY1, the NIH reached out to me to see if there was a way that they could integrate social media into their Undiagnosed Disease Program. Unfortunately, the NIH can't (or won't) set up anything right now. There's an urgent need for this too: genome sequencing is going to unearth the raw data necessary to discover thousands of new genetic disorders like NGLY1 deficiency over the next decade. But, if that data stays isolated, those discoveries just won't happen. Kids won't get diagnosed. If only there were a site full of technically minded entrepreneurs that we could share this opportunity with...
- refurb 12y ago
  Have you reached out to NORD (National Organization for Rare Diseases)? They don't have a website for connecting patients with rare diseases, but they are a pretty well run organization that help connect people the old fashion way.
- eric_bullington 12y ago
  Hi Matt, I've been inspired to start setting up something myself. Long story why, but in short I've got kids of my own around Bertrand's age (also, my own son is named after famous scientist and thinker). They were born healthy, and can't imagine going through what you all have. Also, pre-software development, I did grad school in public health (lots of epi and biostat in a dept of inhl health) and briefly worked in health research. So I may be in a good position to help out. I'm in the process of setting up something using Flask right now and will soon (next few hours) open source it on Github and open it up for contributions. I can't absolutely guarantee that I'll be able to maintain it long-term, but I can certainly get a forum, site, and member registry database up and going and open sourced. Hopefully in such a way that it could be managed by a non-programmers (I realize you have such skills but you obviously have your plate full). Perhaps eventually it could bloom into a full registry of genetic data, pending resolution of privacy issues (maybe using something like dnasubway). I'd really love to team with an established designer(s) on this. I can hack up a UI, but would be best to team with a designer(s). I'd also love to team up with other devs who are interested. Would sociallyrare.org be an ok name for a social media hub for rare diseases? I went ahead and registered that name, but if you have any other suggestions/requests I'd love to hear them. Not sure if Socially Rare has the right ring to it.

Caldercho 12y ago

Such an inspiring story.

TeMPOraL 12y ago

Matt's struggle to find the cause and cure of his son's disease reminded me of a post I read sometime ago: http://lesswrong.com/lw/gvi/metamed_evidencebased_healthcare/ http://lesswrong.com/lw/gvi/metamed_evidencebased_healthcare... While probably not applicable in this case, I think many people struck with rare/weird diseases could find this service useful. MetaMed is basically a group of people who are really good at maths, know the newest medical technologies and procedures, and are willing to dig through and evaluate tons of medical papers and publications. I hope that this will help someone. I'm also interested if anyone on HN used this service and could tell how it worked out in their case.

timsally 12y ago

There are no words for this; an incredible story. My thoughts and prayers are with Bertrand and others with NGLY1 deficiency. It seems that while Professor and Christina Might were making a herculean effort to discover and fight NGLY1 deficiency, Professor Might was granted tenure (!) at the University of Utah and is considered a rising star (http://admin.utah.edu/academic_affairs_posts/rising-stars-at-the-u-2 http://admin.utah.edu/academic_affairs_posts/rising-stars-at...). I doubt anyone makes excuses for late homework in his class.

mattmight 12y ago
Thanks for the kind words and the nod, but I can assure you that there's still no shortages of excuses for late homework. Since this is HN, I'll share one thing that works: force your students to use git (or some version control) for assignments. Having an auditable history of effort makes it hard to lie. Except when it turns "the dog ate my homework" into "git rebase ate my homework."
- ph0rque 12y ago
  "My dog forked my homework."
- nitrogen 12y ago
  There's still the reflog for that excuse (e.g. .git/logs/refs/heads/master).
  - cookiecaper 12y ago
    Only sometimes. There are several actions that may purge items from and/or completely clear the reflog.

lilsunnybee 12y ago

> Patient-advocacy groups have been around for decades, but it’s extremely unusual for one or two families to single-handedly direct an international research agenda. It helps that both the Mights and the Wilseys have family money. (Matt Might’s father is the president and C.E.O. of Cable One, the cable-television division of the former Washington Post Company.) It's a really sad fact that economic inequality has a particularly dire effect on limiting access to quality healthcare and specialists for patients with rare diseases, no matter the severity. The diagnosis difficulties the Mights went through with their son are made much worse for parents who can't pay, even for much more common rare diseases. Hopefully someday our civilization can advance to the point where economic means matter much less than they do now for healthcare, where quality of life and opportunity to thrive is respected equally for every human, regardless of family money, or who gets the right to publish.

thinkcomp 12y ago

Question for Matt (or anyone who knows): What's the best or most cost-effective way to get an entire family sequenced? My younger brother has a rare disorder (diagnosed as autism and twelve other things that mean "we're not sure"), I don't have it, and we've wanted to get everyone sequenced for some time. Any thoughts would be appreciated.

mattmight 12y ago
You may want to check out LineaGen: http://www.lineagen.com/ http://www.lineagen.com/ It's cheaper than sequencing, and more importantly, they actually know what to do with the data once they have it. Getting your sequencing data is becoming cheaper and cheaper. Analyzing it is not.

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gcb0 12y ago

all the best to the families. but this makes me furious at how research is done. everyone pays high tuition and dont think about it. just being glad their families can afford. but you (everyone here probably) is fostering this. expensive pedigree universities are the ones that create such toxic environment for open research. very similar to this was already documented in the "Lorenzo's oil" book/film. lets hope this time we learn the lesson. (yeah, high hopes of anyone here not favoring a Stanford student but anyway ...i have no idea how even start to break this vicious circle that promote inefficient research in that way... maybe killing patents will be the light?)

QuantumChaos 12y ago
I see two separate phenomena. The article describes researchers being rewarded for their publications, and therefore not sharing data with their competitors, who could create a publication with that data which the researcher who shared the data would get no credit for. You are describing people favoring graduates from top universities, which therefore charge higher tuition since their degrees are more valuable. I can't see any relationship between these two things, maybe you can clarify.
- gcb0 12y ago
  the top universities are top universities because of what? the standard metric is number of published papers. So a university to on the top have to play by those rules. and we keeping regarding them as the top are by consequence valuing those rules. the hypocrisy has to end somewhere. We can't keep up voting those articles that point the problems with academic publishing while giving priority to hire from the institutions that maintain that status quo.

gravedave 12y ago

Wish there was a cliffnotes version of this long-winded article. Best of luck to the kid though.

Herdinger 12y ago

I suffer from a condition called visual snow. I realized about ten years ago that what I was expering wasn't normal. The condition was completly unknown at the time and I got multiple MRI's, my eyes and nervous system checked out from every angle and there was nothing abnormal. Talking with many people I know it turned out that this condition is surprisingly pretty common, though in a mild form. People told me they saw some form of constant noise too but dismissed it as normal. Your article got me to check the condition out again and it turns out there is new research from May identifing something wrong with the brain of people under the condition. It's nothing life threatening like you're story, but still it's something you have to learn to live with it's there 24/7 even when you close your eyes and can be imparing at night. http://www.eyeonvision.org/news/107-visual-snow-research-study.html http://www.eyeonvision.org/news/107-visual-snow-research-stu... http://en.wikipedia.org/wiki/Visual_snow http://en.wikipedia.org/wiki/Visual_snow Sadly I'm not in the US and there don't seem to be any research studies in Germany. Therefore I want to shout out if anyone on HN suffers from this condition, maybe hasn't even realized it because it manifests in mild form. You can all help the understanding of the condition.

merlish 12y ago
Oddly, I think I have this. I've tried to explain the vague faint multi-colour noise that overlays my vision that is especially noticeable at night to e.g. my parents before, and they didn't get it. I've always assumed it's normal and that I just failed to explain sufficiently. Reading the wiki article: > In addition to visual snow, many sufferers have other types of visual disturbances such as starbursts, increased afterimages, floaters, trails, and many others.[9] eh maybe; I have no frame of reference >Non-visual symptoms such as tinnitus, depersonalization-derealization, fatigue, speech difficulties and cognitive dysfunction (brain fog) are frequently encountered.[citation needed] Secondary psychiatric sequelae such as anxiety, panic attacks or depression may develop and necessitate appropriate treatment.[citation needed] Tinnitus: Yes, sometimes it flares up a bit for about half an hour before going away again. There's a background level of ringing in an even slightly quiet environment, but I'm not sure if it's just the blood rushing through my ears. I also like listening to music at a loud volume (I find it hard to enjoy music otherwise.) Depersonalization-derealization: Not sure. See 'depression' below. Fatigue: Yes, which I've associated with my depression Speech difficulties: I stutter and find it hard to remember names, but if I'm presenting something you would never realize either of these. Cognitive dysfunction: Quite possibly. If I'm in a more depressed mood, I can't think. Anxiety/panic attacks/depression: I was diagnosed with clinical depression a couple of years ago, when it got so bad I stopped caring about anything and went to a doctor. Headaches/migraines: It varies wildly, but I do get headaches quite badly on occasion. I put this down more to stress & depression.

ryansmurphy 12y ago

TOO MANY ONIONS..... Them dam feels

tuxguy 12y ago

Original article on Bertrand & how Matt Might investigated the cause of Bertrand's illness http://matt.might.net/articles/my-sons-killer/ http://matt.might.net/articles/my-sons-killer/

greenpinguin 12y ago

Amazing story!

xiaoma 12y ago

The actual title of the article is One of a kind.