Pharmacological dosages of pyridoxine have been used to effectively treat seizures in pyridoxine-dependent epilepsy (PDE). PDE is caused by a deficiency of alpha-aminoadipic semialdehyde dehydrogenase resulting in impaired lysine degradation and subsequent accumulation of alpha-aminoadipic semialdehyde. Devastating outcomes including significant developmental delay and intellectual disability have been reported in individuals with PDE despite pyridoxine therapy.

We describe a female child diagnosed with PDE who responded significantly to a combined therapeutic approach using a lysine-restricted diet in conjunction with pyridoxine and folinic acid.

The child presented at 10 days of age with refractory seizures. The EEG was very abnormal and the MRI showed diffusely abnormal white matter .Urine piperideine-6-carboxylate and pipecolate were significantly increased. Genotyping revealed two heterozygous mutations (c.1195G>C, c.1429G>C) in the ALDH7A1 gene.  Aggressive dietary management was commenced within the first two weeks of life with a lysine restriction of 70 mg/kg/d using a combination of expressed breast milk and a lysine-free infant formula. Pyridoxine and folinic acid were supplemented at 30mg/kg/d and 4.5 mg/kg/d respectively. Lysine restriction was tolerated with impressive compliance. Plasma lysine remained in the lower range with a mean concentration of 70 µmol/L (NR 52–196 µmol/L). Post dietary intervention, clinical seizures remained absent and the EEG showed significant improvements by two months of age. Antiepileptic medications were ceased by four months of age. At three years, the child showed a near normal developmental quotient with mild expressive language delay.

Lysine-restricted diet is an effective adjunct in the early intervention of PDE.