Clinical and metabolic consequences of L-serine supplementation in hereditary sensory and autonomic neuropathy type 1C.
Cold Spring Harb Mol Case Stud
; 3(6)2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-29042446
ABSTRACT
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 (SPTLC2) 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-Marie-Tooth 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.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Serina
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Neuropatias Hereditárias Sensoriais e Autônomas
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Serina C-Palmitoiltransferase
Limite:
Adult
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Female
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Humans
Idioma:
En
Revista:
Cold Spring Harb Mol Case Stud
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Finlândia