Early-onset vitamin B6-dependent epilepsy due to pathogenic PLPBP variants in a premature infant: A case report and review of the literature

Abstract

Vitamin B₆-dependent epilepsies are a heterogeneous group of disorders characterized by decreased availability of the active cofactor pyridoxal-5'-phosphate (PLP). While pathogenic variants in ALDH7A1 or PNPO genes account for most cases of these disorders, biallelic pathogenic variants in PLPBP have been shown to cause a form of early onset vitamin B₆-dependent epilepsy (EPVB6D). PLPBP is thought to play a role in the homeostatic regulation of vitamin B₆, by supplying PLP to apoenzymes while limiting side-reaction toxicity related to excess unbound PLP. Neonatal-onset intractable seizures that respond to pyridoxine and/or PLP are a predominant feature of EPVB6D in humans. Unlike other causes of vitamin B₆-dependent epilepsies; however, a specific biomarker for this disorder has yet to be identified. Here we present data from a premature infant found to have pathogenic variants in PLPBP and propose that prematurity may provide an additional clue for early consideration of this diagnosis. We discuss these findings in context of previously published genotypic, phenotypic, and metabolic data from similarly affected patients.

Keywords: PLPBP; PLPHP; PROSC; prematurity; pyridoxal‐5′‐phosphate; pyridoxine; vitamin B6‐dependent epilepsy.

FIGURE 1

Brain magnetic resonance imaging in our patient day 6 day of life (corrected gestational age 35⁺³weeks). A, Sagittal T2 weighted image demonstrates small cerebrum and cerebellum with very thin corpus callosum. B and C, Axial T2 weighted images demonstrate simplified gyral pattern with thin lissencephalic cortex more severe in the frontal lobes (thick arrows), decreased white matter volume with markedly abnormal T2 hyperintensity, bilateral periventricular cysts (thin arrows) with blood products in the large left sided cyst and in a tiny right sided cyst (arrowheads). Prominent ventricles and large extra‐axial CSF spaces in keeping with small brain