December 17, 2009

Case Reopened

Bertrand's positive response to the ketogenic diet kicked off a flurry of emails among his medical team at the University of Utah. It seems that efforts to diagnose him are being renewed. Here are some excerpts from emails today.

From Neurology:
[addressing genetics]
Could you help review whether the following causes of metabolic epilepsies that present with infantile onset of myoclonus have been tested?: cerebral glucose transporter (GLUT1) deficiency, pyridoxine dependent epilepsy, neuronal ceroid lipofuscinosis, cathepsin D deficiency, mitochondrial disease such as Alpers syndrome (POLG deficiency), Gaucher disease type 3, and guanidinoacetate methyltransferase (GAMT) deficiency. I think Dravet's is also on the list with SCN1A mutations (although he did not present with prolonged febrile seizures which is classic for this disease). I am not sure the LFT abnormalities are a result of the seizures or whether they are a separate phenomenon due to an inborn error of metabolism. Unfortunately, I did not ask for a serum glucose when the CSF glucose was drawn back in April, but the CSF glucose was not <50.>

From Genetics:
[responding to neurology]
1. cerebral glucose transporter (GLUT1) deficiency: not sure: glucose and lactate were normal in CSF (they are usually low).
2. pyridoxine dependent epilepsy: normal PLP in CSF
3. neuronal ceroid lipofuscinosis: normal enzyme assay for types 1 and 2. Others types are possible
4. cathepsin D deficiency: possible, would investigate together with ceroid lipofucsinoses other that 1 or 2 if the ERG shows specific abnormalities (he had not done this at time of our last visit),
5. mitochondrial disease such as Alpers syndrome (POLG deficiency): this is possible: I have not seen him in a while, but he has liver involvement and brain involvement. Would send mtDNA depletion panel
6. Gaucher disease type 3: there is no real hepatosplenomegaly that is severe in patients with types 2 or 3
7. guanidinoacetate methyltransferase (GAMT) deficiency: the MR spectroscopy done at DUKE had all sort of pseudoanomalies, but creatine was NOT reported as abnormal.

Unfortunately, there are several conditions that respond to ketogenic diet without a specific reason, in addition to GLUT1 and PDH deficiency.

Depending on how this child is progressing (if he is doing better as he was at his last visit, would doubt mtDNA depletion syndrome) would proceed with DNA testing for mtDNA depletion syndromes (all of them present similarly) and some of the neuronal ceroid lipofucsinoses (depending on how well he can see). Dravet syndrome is a possibility for me as well and would fit with the minimal abnormalities found in the brain MRI.

This email volley has made me hopeful that perhaps 2010 will finally bring a diagnosis for Bertrand! And, perhaps we can start planning for the future of our family.

Oh, and I didn't forget. Here, as promised, is the video of Bertrand in week 5 of the ketogenic diet.


  1. That's very exciting! :-) Plenty more positive thoughts headed your way!

  2. That will be such a relief to have some closure on that. And he is such a sweetheart :-)

  3. Hi Christina & Matt, Quick introduction: I came across your son's site as a result of an ongoing Google search tagged with Inborn Errors of Metabolism and Cerebral Organic Acidemia. I have both because of a missing enzyme in my metabolic pathway which was just diagnosed in 2005. This is the reason it is believed for my epilepsy. There is much more to this story and search for answers as you well know. The Inborn Errors of Metabolism your son and I are challenged with are not similar other than the likely cause of our seizures. With that said have you checked out the Organic Acidemia Association for support and as another resource?
    Sincerely, Craig

  4. You may already be aware of these doctors but in case not, you never know.....

    Have your medical team (or you as a start)contact Dr. Jean-Marie Saudubray and Dr.
    Frederic Sedel in Paris. Dr Sedel is the email gatekeeper for Dr. Saudubray and is very easy to work with. They are the worlds best with Epilepsy & Inborn Errors of Metabolism.

    Departement des maladies métaboliques, Federation des maladies du système
    nerveux,Hopital Pitié‐Salpêtrière et Université Pierre et Marie Curie (Paris VI), 47 boulevard
    de l’hopital,75651 Paris cedex 13, France

    In the USA the Cleveland Clinic would be another good resource for Epilepsy & Inborn Errors of Metabolism with Dr Emily Oby and Dr. Damir Janigro. I do not have their contact info handy but just do a search and they will pop up.

  5. Great video! I also love Elmo!
    Titi Lili

  6. Wow, Craig! Thank you!!! We will bring up the doctors you mentioned at B's genetics appt. on Monday! I look forward to learning more about organic acidemias--something tells me I won't have a choice in the matter.

  7. Cristina, how awesome would that be?!! I know how much you have fought tooth-and-nail-and-more to get the doctors to get some answers.

    I had to chuckle at the GD3 listing. You probably know more about GD3 than they do!

    What Craig said was very interesting -- keep me updated on that.

    I can't believe how great he is doing on his stander.

    Something tells me that 2010 will be a great year for B and your family :)

  8. "Here is an additional resource about the genetics of GLUT1 Deficiency Syndrome: I hope it helps. Thanks, AccessDNA"