Biochemical Spectrum and Clinical Outcomes of Symptomatically Detected Pyridoxine-Dependent Epilepsy in the Indian Population

Ketki Vinod Kudalkar, Umamaheswari Balakrishnan, Pranathi Gutta, Chinthalapalli Prakash Ravi Kumar, Sivaprakasam Balaji, Rajesh Karuvattil, Singara Velmurugan, Anil Bansidhar Jalan

Abstract

Mutations in the antiquitin (ALDH7A1) gene cause pyridoxine-dependent epilepsy (PDE). It is a rare autosomal recessive epileptic encephalopathy (OMIM# 266100). The prevalence is estimated at 1 in 400,000 to 700,000 neonates. It affects lysine catabolism, resulting in accumulation of pipecolic acid, α-aminoadipic semialdehyde, and pyrroline-6ʹ-carboxylate. Clinically, it presents as neonatal refractory epilepsy, which responds to pharmacologic dose of pyridoxine.

We herewith present the phenotypic, genotypic, and biochemical spectrum of 11 cases (8 males and 3 females) with ALDH7A1 deficiency. The most common presenting symptoms include neonatal epilepsy, respiratory distress, and irritability. One case had hydrocephalus along with refractory epilepsy. Biochemical and genetic studies were performed to confirm the diagnosis. We also discuss the treatment options and outcomes in each of these cases.

The phenotypic spectrum of PDE includes a myriad of symptoms. As this disorder is amenable to treatment with pyridoxine, folinic acid, arginine, and a lysine-restricted diet, it is essential to diagnose the disorder early in life for better outcomes. All neonates who present with unexplained epilepsy should be screened for antiquitin deficiency.