Deoxysphingolipids as candidate biomarkers for a novel SPTLC1 mutation associated with HSAN-I.

Abstract

Hereditary sensory and autonomic neuropathy type 1 (HSAN-I)—an autosomal dominant, mainly sensory neuropathy—typically affects patients in their second and third decades, presenting with ulcerations and lancinating pain attacks.1 Diagnosis is heavily dependent on genetic analysis, focusing on 6 genes: serine palmitoyltransferase ( SPT ) long chain base subunits 1 and 2 ( SPTLC1 and SPTLC2 ), atlastin 1 ( ATL1 ) and 3 ( ATL3 ), DNA methyltransferase 1, and Ras-related protein ( RAB7 ). Most patients carry SPTLC1 mutations (OMIM*605712) that affect sphingolipids biosynthesis by modifying SPT substrate specificity to produce atypical neurotoxic deoxysphingoid bases (DSBs). Along with their accumulation in mutant cells, elevated DSBs were also found in plasma samples, thus becoming a candidate biomarker of disease.2