PYRIDOXINE DEPENDENT EPILEPSY

ALDH7A1 GENE ANALYSIS IN PYRIDOXINE DEPENDENT EPILEPSY

Pyridoxine dependent epilepsy (PDE) is an autosomal recessive epileptic encephalopathy characterised by a therapeutic response to pharmacological dosages of pyridoxine (vitamin B6) and resistance to conventional antiepileptic treatment. Typically PDE presents with neonatal or early infantile seizures and despite seizure control most patients have intellectual disability. Seizures recur upon pyridoxine withdrawal.

PDE is caused by homozygous or compound heterozygous mutats in the ALDH7A1 gene (Mills et al. 2006 Nat Med 12:307-309; Salomons et al. 2007 Ann Neurol 62:414-418).

The ALDH7A1 gene encodes a-aminoadipic-semialdehyde dehydrogenase which is part of the lysine catabolism pathway in the brain and liver. Biochemically patients with PDE have elevated levels of a-aminoadipic-semialdehyde in urine, plasma and Cerebrospinal Fluid, and an elevated level of Pipecolic acid in plasma (Stockler et al. 2011 Mol Genet Metab 104:48-60).

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.