SPTLC1 has been implicated in hereditary sensory and autonomic neuropathy type 1 (HSAN1) and macular telangiectasia type2. Recent studies have reported mutations in SPLTC1 may cause juvenile amyotrophic lateral sclerosis (JALS), especially in the first transmembrane domain of SPTLC1(exon 2). In this study, we identified a novel heterozygous variant in exon 2, c.113 T > C: p. Leu38Arg, of SPTLC1 in a 12-year-old girl with sporadic JALS who experienced early-childhood-onset lower extremity spasticity followed by slowly progressive lower motor weakness and atrophy without sensory symptoms or signs. SPLTC1 is the first monogenic lipid metabolic disturbance that has been linked to ALS. The variant in exon 2 may impact on negative regulation of sphingolipid biosynthesis.
Keywords: Genetics; SPTLC1; genotype; juvenile amyotrophic lateral sclerosis; phenotype.