ASAH1 Variants Causing Spinal Muscular Atrophy Phenotype

Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a rare autosomal recessive disorder due to mutations in the ASAH1 gene. SMA-PME is characterized by progressive muscle weakness from three to seven years of age, drug refractory epilepsy, and variable degree of cognitive decline. Nearly 50 cases have been reported worldwide so far. Here the authors present a case of 9-y-old boy affected by SMA-PME characterized by progressive proximal weakness, and lower motor neuron disease, as proven by muscle biopsy, electro diagnostic studies and whole exome sequencing (WES). WES revealed compound heterozygous missense variant in exon 12 of ASAH1 gene (chr8: g.18059385G>C) and exon 2 of ASAH1 gene (chr8: g.18075542T>C). Patient did not have cognitive decline and epilepsy and EEG record obtained was normal. In addition to reporting a novel variant in the ASAH1 gene causing SMA-PME disease, this paper discusses previous reports and literature of the disease.