Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is an inherited peripheral neuropathy characterised by marked sensory loss, variable motor involvement and frequent complications. Mutations in the SPTLC1 gene are responsible for this disorder. Mutant SPTLC1 is associated with the accumulation of two atypical deoxy-sphyngoid bases (dSBs) which produce a toxic effect in cultured sensory neurons. dSB levels are elevated in plasma of patients with HSAN1 and transgenic mice. L-serine is a potential therapy for HSAN1, however the lack of natural history studies and outcome measures are major barriers to a clinical trial. This cross-sectional study has been conducted to fully characterise the phenotype of HSAN1 and to establish correlation of plasma dSBs with disease severity. We obtained detailed clinical data in a cohort of 20 SPTLC1/ HSAN1 patients. Clinical impairment was assessed by the Charcot Marie Tooth Neuropathy score (CMTNS). Onset occurred in the second and third decade in the majority of patients. Males showed a more severe disease course compared to females. Neuropathic pain was present in 70% of patients. Sensory complications were observed in 80% of patients. dSBs were significantly elevated in all patients and correlate with disease severity. This cross-sectional study highlights the role of dSBs as a potential marker for disease severity. A longitudinal study to establish whether dSBs can be used as biomarker of progression of disease is warranted.
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