Abstract
Antiquitin deficiency is the most prevalent form of pyridoxine-dependent epilepsy.
While most patients present with neonatal onset of therapy-resistant seizures, a few
cases with late-onset during infancy have been described. Here, we describe the juvenile
onset of epilepsy at the age of 17 years due to antiquitin deficiency in an Indian
female with homozygosity for the most prevalent ALDH7A1 missense mutation, c.1279G > C;
p.Glu427Gln in exon 14. The diagnosis was established along familial cosegregation
analysis for an affected offspring, that had neonatal pyridoxine responsive seizures
and had been found to be compound heterozygous for c.1279G > C; p.Glu427Gln in exon
14 and a nonsense mutation c.796C > T; p.Arg266* in exon 9. While seizures in the
mother had been incompletely controlled by levetiracetam, she remained seizure-free
on pyridoxine monotherapy, 200 mg/day. Her fourth pregnancy resulted in a female affected
offspring, who was treated prospectively and never developed seizures with a normal
outcome at age 2 years while on pyridoxine. This report illustrates that the phenotypic
spectrum of antiquitin deficiency is still underestimated and that this treatable
inborn error of metabolism has to be considered in case of therapy-resistant seizures
even at older age. It furthermore supports prospective in utero treatment with pyridoxine
in forthcoming pregnancies at risk.
Keywords
late-onset - genotype -phenotype - intrauterine treatment - prenatal - PDE - therapy
resistance
