Phenobarbital Toxicity Due to Poor Metabolism in a Neonate with Pyridoxine-Dependent Developmental and Epileptic Encephalopathy: A Case Report - Abstract
Pyridoxine-dependent developmental and epileptic encephalopathy (PD-DEE) is a genetic metabolic disorder with seizures resistant to anti-seizure
medications. We report a case of a male neonate with frequent focal motor seizures onset within the first day of life that were not controlled by conventional
doses of phenobarbital. Moreover, he subsequently developed impaired consciousness and respiratory failure. His seizures stopped after an intravenous
infusion of vitamin B6 at 17 days of age. A metabolic screening at 24 days of age revealed elevated pipecolic acid and he was started on oral vitamin
B6. Genetic testing confirmed his diagnosis of PD-DEE caused by a pathogenic compound heterozygous variant in ALDH7A1. Meanwhile, a significantly
elevated serum phenobarbital concentration was detected. After withdrawal of phenobarbital, his consciousness and respiration gradually returned to normal.
Pharmacogenomic testing revealed that he carried several single nucleotide polymorphisms such as ABCB1 and SCN2A and was a poor metabolizer of
phenobarbital, which explained the occurrence of toxicity. He was followed up to the age of 2 years and had no seizures or neurological sequelae with vitamin
B6 supplementation. The case suggests that pharmacological doses of vitamin B6 are recommended in early-onset seizures, and genetic testing should be
performed timely to identify the etiology and guide treatment decisions. Pharmacogenomic testing may be considered to guide individualized treatment when
drug efficacy and adverse effects are significantly inconsistent with dosage and expectations