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.