Monday, February 04, 2008

Succinic semialdehyde dehydrogenase deficiency (SSADH)

Pearl PL, Gibson KM, Acosta MT, et al. Clinical spectrum of SSADH. Neurology 2003; 1413-1417.

Or, how to have at least a little familiarity with this entity. This is based on a review of 51 patients, ages 1-21 at diagnosis.SSADH is also called 4 hydroxy butyric aciduria.

The presentation during childhood is psychomotor seixures, hypotonia, and nonprogressive ataxia, disproportionate language impairment, behavioral abnormalities including aggressiveness, anxiety, hallucinations, and self injurious behavior. Developmental delay, hypotonia, and mental retardation are the major clinical manifestations. Ataxia, behavior problems seizures and hyporeflexia appear in slightly less than half, and the syndrome is slowly or nonprogressive.

EEG shows generalized and focal epileptiform activity, photosensitivity, background slowing,sleep asynchrony, and was normal in about half. MRI showed T2 hyperintensities in the globus pallidus bilaterally and symmetrically.

The treatment is obscure-- the authors discuss the rationale of vigabatrin (nonapproved) in the GHB pathway , notes the Depakote is contraindicated as it inhibits any remaining SSADH. Naloxone reverses GHB-mediated inhibitory effect on striatal dopamine release.

Biochem--SSADH + GABA transaminase convert GABA to succinic acid. In SSADH, GABA instead converts to 4-hydroxybutyrate. GHB accunulates in urine, serum, and CSF of patients. The gene maps to chromosome 6p22. Standard organic acid screens miss the increased excretion of 4-oh- butyric acid. Only a small peak obscured in a large urea peak may appear. It is necessary to add a selective ion monitoring mass spectrometry screen for specific compounds to make the diagnosis.

GHB is an endogenous metabolite and neurotransmitter. It is used to manage cataplexy and opiate and alcohol withdrawl, as a recreational drug of abuse, and to subdue victims for sexual assault. Please see related posts on GHB and toner cartridge abuse.

1 comment:

shashank said...

Here is a link to more information about the genetics of Succinic Semialdehyde Dehydrogenase Deficiency that was prepared by our genetic counselor and which has links to some useful resource for those dealing with this condition: There is also a number listed for anyone who wants to speak to a genetic counselor by phone. I hope it helps. Thanks, AccessDNA