Serine Palmitoyltransferase And Peripheral Neuropathy: Studies On Neuropathy-Causing Mutations And Their Biochemical Hallmarks

The study focused on the enzyme serine palmitoyltransferase (SPT) and its role in hereditary sensory and autonomic neuropathy type 1 (HSAN1), a condition caused by mutations in SPT subunits SPTLC1 and SPTLC2. These mutations led to increased production of neurotoxic 1-deoxysphingolipids (1-deoxySLs), which are linked to the disease's symptoms. The research identified 13 missense mutations associated with HSAN1, highlighting significant genotypic and phenotypic variability. A notable case involved a new mutation (p.S331Y) causing severe symptoms. The study demonstrated that dietary L-serine supplementation effectively reduced 1-deoxySL levels and improved symptoms in patients, suggesting it as a promising long-term therapy for HSAN1. The research also indicated that mutations in SPTLC1 and SPTLC2 might not be the sole cause of increased 1-deoxySLs, pointing to a complex mechanism requiring further investigation.