Clinical and metabolic consequences of L-serine supplementation in hereditary sensory and autonomic neuropathy type 1C.

摘要: Hereditary sensory neuropathy type 1 (HSAN1) may be the first genetic amenable to a specific mechanism-based treatment, as L-serine supplementation can used lower neurotoxic levels of 1-deoxysphingolipids (1-deoxySL) that cause neurodegeneration. The treatment is so far untested in HSAN1C caused by variants serine palmitoyl transferase subunit 2 (SPTLC2) gene. aim this study was establish whether oral lowers 1-deoxySL patient with HSAN1C, perform dose escalation find minimal effective dose, and assess safety profile global metabolic effects treatment. Our underwent 52-wk which titrated up 400 mg/kg/day. She followed repeated clinical examination, nerve conduction testing, skin biopsies document on small fibers. Serum assayed for metabolomics analysis 111 metabolites. We found robust lowering 1-deoxySL, correlated near-linear fashion increased serum levels. Metabolomics showed modest elevation glycine marked reduction level cytosine, whereas most other metabolites did not change. There were no direct side from but developed transitory toe ulceration during course study. Charcot-Marie-Tooth score point. conclude decreases without major metabolism. therefore potential HSAN1C.