{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T23:05:59Z","timestamp":1775603159185,"version":"3.50.1"},"reference-count":25,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2017,11]]},"abstract":"<jats:p>Hereditary sensory neuropathy type 1 (HSAN1) may be the first genetic neuropathy amenable to a specific mechanism-based treatment, as L-serine supplementation can be used to lower the neurotoxic levels of 1-deoxysphingolipids (1-deoxySL) that cause the neurodegeneration. The treatment is so far untested in HSAN1C caused by variants in the serine palmitoyl transferase subunit 2 (<jats:italic>SPTLC2<\/jats:italic>) gene. The aim of this study was to establish whether oral L-serine lowers 1-deoxySL in a patient with HSAN1C, to perform a dose escalation to find the minimal effective dose, and to assess the safety profile and global metabolic effects of the treatment. Our patient underwent a 52-wk treatment in which the L-serine dose was titrated up to 400 mg\/kg\/day. She was followed up by repeated clinical examination, nerve conduction testing, and skin biopsies to document effects on small nerve fibers. Serum was assayed for 1-deoxySL and metabolomics analysis of 111 metabolites. We found a robust lowering of 1-deoxySL, which correlated in a near-linear fashion with increased serum L-serine levels. Metabolomics analysis showed a modest elevation in glycine and a marked reduction in the level of cytosine, whereas most of the other assayed metabolites did not change. There were no direct side effects from the treatment, but the patient developed a transitory toe ulceration during the course of the study. The Charcot\u2013Marie\u2013Tooth neuropathy score increased by 1 point. We conclude that oral supplementation of L-serine decreases 1-deoxySL in HSAN1C without major global effects on metabolism. L-serine is therefore a potential treatment for HSAN1C.<\/jats:p>","DOI":"10.1101\/mcs.a002212","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T00:55:17Z","timestamp":1508288117000},"page":"a002212","source":"Crossref","is-referenced-by-count":34,"title":["Clinical and metabolic consequences of L-serine supplementation in hereditary sensory and autonomic neuropathy type 1C"],"prefix":"10.1101","volume":"3","author":[{"given":"Mari","family":"Auranen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jussi","family":"Toppila","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saranya","family":"Suriyanarayanan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Museer 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