HMSN-6B

SLC25A46 | 2015

What Is HMSN-6B?

HMSN-6B is a type of CMT caused by autosomal recessive mutations in the SLC25A46 gene. This gene provides instructions for making a mitochondrial membrane protein that regulates the shape and distribution of mitochondria within nerve cells. Mutations in the SLC25A46 gene disrupt this function, leading to impaired nerve signal transmission.

HMSN-6B is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.

Clinical Features

The age of symptom onset in HMSN-6B is variable, ranging from childhood to adulthood. Symptoms typically begin in the lower extremities and progress over time to involve the upper limbs. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.

HMSN-6B symptoms may include:

  • Weakness in the feet and lower legs
  • Muscle atrophy
  • Foot drop
  • Reduced or absent reflexes
  • Reduced sensation
  • A steppage-style walking pattern
  • Foot deformities, including high arches, and hammertoes (clawed toes)
  • Progressive involvement of the hands and forearms
  • Difficulty with fine motor skills and manual dexterity
  • Additional symptoms not listed here

Disease Course

HMSN-6B 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
HMSN-6B

Classification
HMSN

Neuropathy Type
Axonal

Inheritance Pattern
autosomal recessive

Genetic Context

HGNC-Approved Gene Symbol
SLC25A46

Gene Full Name
Solute Carrier Family 25 Member 46

Chromosome
5q22.1

Zygosity of Responsible Variant
Homozygous or Compound Heterozygous

Mitochondrial Involvement
Yes

Variant Mechanism
Loss of Function (LoF)

ClinVar Pathogenic Variants

View HMSN-6B ClinVar Variants

HMSN-6B OMIM Entry

HMSN-6B OMIM

SLC25A46 OMIM Entry

SLC25A46 OMIM

More Info

HMSN-6B Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Mutations in SLC25A46, Encoding a UGO1-Like Protein, Cause an Optic Atrophy Spectrum Disorder

Authors

Abrams, A. J., Hufnagel, R. B., Rebelo, A., Zanna, C., Patel, N., Gonzalez, M. A., Campeanu, I. J., Griffin, L. B., Groenewald, S., Strickland, A. V., Tao, F., Speziani, F., Abreu, L., Schüle, R., Caporali, L., La Morgia, C., Maresca, A., Liguori, R., Lodi, R., Ahmed, Z. M., … Dallman, J. E.

Publication Date
July 13, 2015

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

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