Child Neurology: Severe <i>GMPPB</i>-Related Congenital Muscular Dystrophy With Rapidly Progressive Encephalopathy Leading to Infantile Death.

Abstract

Pathogenic variants in <i>GMPPB</i> cause congenital muscular dystrophy through hypoglycosylation of alpha-dystroglycan (OMIM #615350). The established phenotypic spectrum of GMPPB-related disorders includes recurrent rhabdomyolysis, limb-girdle muscular dystrophy, neuromuscular transmission abnormalities, and congenital muscular dystrophy with variable brain and eye anomalies. We report a 9-month-old male infant with congenital muscular dystrophy, infantile spasms, and compound heterozygous pathogenic variants (c.624T>G and c.1000G>A) in <i>GMPPB</i> who presented acutely in status epilepticus progressing to refractory hemodynamic instability and multiorgan failure leading to death 20 days after admission. Brain MRI showed a pattern of symmetric diffusion restriction consistent with possible vigabatrin toxicity and progressive cerebral volume loss. Postmortem neuropathology examination confirmed features of dystroglycanopathy including patchy loss of dystroglycan staining of muscle. This report of infantile death in an individual with a <i>GMPPB</i>-related disorder raises concern for potential risk of early mortality possibly exacerbated by vigabatrin toxicity.