Ezra’s life story could fill a book – he’s not yet 4. But, if you fast forward just a bit, it leads us to this:
February 4, 2016. “Greetings. Thanks for doing the exome testing. We would like to see Ezra to discuss results […]”: said (the cryptic) email from Dr. J., our Clinical and Metabolic Geneticist, Director of Neurogenetics/Metabolic Program. My heart immediately skip a beat… or three.
3 years of testing and we might have an answer?
“OMG! What do you think she means by this email”, I asked papabear once or twice (read: about once an hour leading up to our appointment)? “Is there a hidden code in the message?”
February 10, 2016. 3 kids (1 nursling and 2 kiddo patients), 2 grandparents (thank you!!), a large bag of goodies and lunch and diapers and wipes, one anxious mamabear and one car sickness moment later, we arrived to hear the news from the genetic and neurology team.
“We got the results back – the good news is we don’t know what it means, and the bad news is we don’t know what it means either.” (paraphrasing much?) But seriously, that’s essentialy the answer we got. They left us with a follow up plan and encouragement to reach out however and to whoever we can to find more to our answer. And, that they will do the same.
As it turns out, Ezra is “patient zero”. Ezra is currently the only human being on this planet known to have P377A and V231I variants on the SAMM50 gene. (And how many people actually have proof of how unique they are?)
Did you click on the link above? If you didn’t – I’ll save you the trouble. Because, there’s only ONE sentence in Wikipedia on the SAMM50 gene. “Sorting and assembly machinery component 50 homolog is a protein that in humans is encoded by the SAMM50 gene.”
March 7, 2016 – Updated Wikipedia to include the following:
By means of exome sequencing, two variants – P377A and V231I on the SAMM50 gene were determined to have a potential relationship to the disease phenotype of Ezra, a 3 year old male with neurodevelopmental disorder, episodes of psychomotor regression, history of macrocephaly and history of torticollis. These variants have not been reported previously, making Ezra the only person known to have these variants.”
You might want a cup of coffee (or a nap) before you read the next paragraph, though. (And no hard feelings if you skip right past it.)
GeneDx (DNA Diagnostic Experts) gave us the following interpretation in our Exome report: “The SAMM50 gene is a candidate gene with a potential relationship to the phenotype. This finding requires further evaluation in a research setting. To date, no pathogenic variants in the SAMM50 gene have been reported in association with a specific human diesease to our knowledge. While the function of SAMM50 has not been completely defined, the literature suggests the SAMM50 gene encodes a component of the SAM complex within the outer mitochondrial membrane, which integrates beta-barrel proteins into the membrane (Humphries et al., 2005; Xie et al., 2007). The SAM complex interacts with the MINOS complex withi the inner mitochondrial membrane, which plays a role in determining mitochondrial cristae morphology (Bohnert et al., 2012; Weber et al., 2013). Therefore, the SAMM50 protein helps bridge the space between the inner and outer mitochondrial membranes and is thought to be essentail for the maintenance of cristae structure (Ott et al., 2012).” Did you get all that? Oh, great! So, can you explain it to me please in English? (Bonus if you don’t have to re-read it 6 times before doing so.)
Our geneticist’s experience and understanding of Ezra’s phenotype, leads her to believe that the variants on the SAMM50 gene are the cause of his challenges. Now, here’s where this website “describingezra.org” comes in.
A few months ago, I reached out to UDN (Undiagnosed Diseases Network) and spoke to a very helpful man named Paul. (Thank you Paul for your listening ear and your kindness.) He encouraged us to reach out to Matt Might, who gave me some very valuable advice – mostly that we need to reach out via social media to search for others like Ezra. Matt recently gave a talk at the White House on precision medicine, utilizing his own story (read it in The New Yorker) to illustrate his message. Just a few years ago, Matt’s son Bertrand was also “patient zero”. But due to his blog post “Hunting down my son’s killer” going viral, there are now 40+ known patients with NGLY1 deficiency around the world who have been able to connect, collaborate and find answers. Thank you Matt for the inspiration!
So, what happened to actually “describing Ezra”, and why we’ve come to this point in our story? Well, that’s something that has been more than 4 years in the making (Ezra will be turning 4 in a few short weeks). So bear with me as I add pertinent information to this blog/website. Such as birth history, symptoms (Updated on March 8, 2016 – Please click for more information) and all that jazz. But let’s just start with the undisputed fact that Ezra looks ridiculously cute in his genes.
And, here we are, optimistically spinning out into the world wide web in the hopes that we find a parent, patient, doctor and/or researcher who types SAMM50 into their search bar for much the same reasons we did. And when you do, wherever you are in this global world of ours – we hope that you reach out. Send it to anyone you think may help or think it may help. Reaching out can lead to confirming a diagnosis and finding real answers. Answers that will help not only Ezra but others as well. Please click here to contact us. And in this global genetic world, I can’t think of a better expression: “Whoever saves a life is as though they have saved an entire world”. Let’s do it together.