HSAN-1A

SPTLC1 | 2001

What Is HSAN-1A?

HSAN-1A is a type of CMT caused by autosomal dominant mutations in the SPTLC1 gene. This gene provides instructions for making part of an enzyme involved in the production of sphingolipids, a class of fats essential to nerve cell membranes. Mutations in the SPTLC1 gene disrupt this function, leading to impaired nerve signal transmission.

HSAN-1A is autosomal dominant, meaning that just one of the gene’s two copies needs a mutation to cause this subtype.

Clinical Features

The age of symptom onset in HSAN-1A is variable, typically in the second or third decade of life. The disease is sensory-predominant, with loss of pain and temperature sensation in the feet that leads to unnoticed injuries. Nerve conduction studies reflect a sensory and axonal process.

HSAN-1A symptoms may include:

  • Progressive loss of sensation in the feet and lower legs
  • Painless injuries and slow-healing foot ulcers
  • Lancinating (shooting) pains in some individuals
  • Reduced or absent reflexes
  • Distal weakness that develops as the disease progresses
  • Foot deformities
  • Foot drop
  • Additional symptoms not listed here

Disease Course

HSAN-1A shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.

Clinical Basics

Subtype
HSAN-1A

Classification
HSAN

Neuropathy Type
Axonal

Inheritance Pattern
autosomal dominant

Genetic Context

HGNC-Approved Gene Symbol
SPTLC1

Gene Full Name
Serine Palmitoyltransferase Long Chain Base Subunit 1

Chromosome
9q22.31

Zygosity of Responsible Variant
Heterozygous

Variant Mechanism
Toxic Gain of Function (GoF)

ClinVar Pathogenic Variants

View HSAN-1A ClinVar Variants

HSAN-1A OMIM Entry

HSAN-1A OMIM

SPTLC1 OMIM Entry

SPTLC1 OMIM

More Info

HSAN-1A Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Mutations in SPTLC1, Encoding Serine Palmitoyltransferase, Long Chain Base Subunit-1, Cause Hereditary Sensory Neuropathy Type I

Authors

Dawkins, J. L., Hulme, D. J., Brahmbhatt, S. B., Auer-Grumbach, M., & Nicholson, G. A.

Publication Date
March 27, 2001

Updated: July 18, 2026 | By: K. Raymond

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