Pyridoxine-dependent Epilepsy: Normal Outcome in a Patient with Late Diagnosis after Prolonged Status Epilepticus Causing Cortical Blindness

Abstract

We report on a male proband with pyridoxine-dependent epilepsy (PDE) and neonatal seizure onset. At the age of 31 months, a prolonged status epilepticus led to severe neurological regression with cortical blindness, loss of speech and muscular hypotonia with slow recovery over the following 3 months. At 33 months of age pyridoxine therapy was initiated with excellent response and the boy remained seizure-free on pyridoxine monotherapy, except for two occasions with seizure recurrence 10 days after accidental pyridoxine withdrawal. alpha-aminoadipic semialdehyde dehydrogenase (antiquitin) deficiency was indicated by elevated pipecolic acid concentrations in plasma and alpha-aminoadipic semialdehyde excretion in urine. Molecular analysis of the antiquitin gene revealed a novel missense mutation c.57insA, while the mutation of the other allele remained unidentified so far. Despite the delay in diagnosis and prolonged status epilepticus, neuropsychological evaluations at the ages of 11 and 18 years demonstrated full-scale IQ of 93 and 92, respectively, with better verbal IQ (103 and 101) than performance IQ (85 and 82).

The genotypic and phenotypic spectrum of pyridoxine‐dependent epilepsy due to mutations in ALDH7A1

“…1 and previously reported mutations are referenced in Table 1 (Mills et al 2006; Plecko et al 2007; Salomons et al 2007; Kanno et al 2007; Kluger et al 2008; Kaczorowska et al 2008; Striano et al 2009; Bennett et al 2009; Gallagher et al 2009; Schmitt et al 2010; Millet et al 2010). There are 26 missense mutations, 13 of which cluster in exons 14, 15, and 16.…”

“…Forty-seven such cases were presented in a recent report from the North American Registry of pyridoxine-dependent epilepsy (groups 1 and 2 in Gospe 2002). A subset of these patients, which we call group 1, have normal developmental outcome, including our patient 1 (8 cases in Basura et al 2009; case C2 in Mills et al 2006; 7/28 cases in Haenggli et al 1991; 1 case in Kluger et al 2008; patient 2 in Striano et al 2009; 3/11 patients in Been et al 2005; 1/6 cases in RamachandranNair and Parameswaran 2005; 2/9 patients with elevated pipecolic acid in Plecko et al 2005; and 1 case in Millet et al 2010). In contrast, the majority of patients with complete seizure control have mild to moderate developmental delays; these we call group 2, which includes patients 2 and 3 reported here.…”

Intragenic deletions of ALDH7A1 in pyridoxine-dependent epilepsy caused by Alu - Alu recombination

“…Case 6 was also previously reported. 7 Array comparative genomic hybridization. We performed array comparative genomic hybridization (CGH) using a custom oligonucleotide array that had 489 probes within the ALDH7A1 gene.…”

Seizures caused by pyridoxine (vitamin B6) deficiency in adults: A case report and literature review

“…This condition may result from dietary deficiency, liver disease, pregnancy and certain medications and can be easily treated by vitamin B6 decarboxylation of glutamine into Gamma-Animobutytic Acid (GABA), a major inhibitory neurotransmitter. A deficiency of PLP leads to decreased GABA concentration in the brain, thereby increasing the risk for seizures (18).…”