SLC5A6 Mutations in Axonal Sensorimotor Polyneuropathy Patients Concurrent With Sodium Dependent Multivitamin Transporter Deficiency and Improved Effects by Multivitamin Therapy

Abstract

Background and Aims

The SLC5A6 gene encodes a transmembrane protein responsible for transporting biotin, pantothenic acid, and lipoic acid. Mutations in SLC5A6 have shown a wide spectrum of clinical phenotypes, such as sodium-dependent multivitamin transporter deficiency (SMVTD), childhood-onset biotin-responsive peripheral motor neuropathy (COMNB), and mixed axonal and demyelinating sensory motor neuropathy. The purpose of this study was to identify pathogenic SLC5A6 mutations in the Korean CMT cohort.

Methods

This study performed whole exome sequencing to identify the genetic cause for two independent patients with early onset axonal sensorimotor polyneuropathy and SMVTD. We also examined the therapeutic effects of multivitamin replenishment on a patient with SLC5A6 mutations.

Results

We identified compound heterozygous variants of SLC5A6 in two patients (p.Arg94X and p.Phe522Ser in patient 1; p.Cys443Tyr and p.Phe513_Lys515delinsLeu in patient 2). In patient 2, an oral regimen comprising biotin, lipoic acid, and pantothenic acid demonstrated significant therapeutic effects, including cessation of cyclic vomiting, resolution of skin lesions on the fingers, and improvements in muscle weakness affecting both the upper and lower extremities.

Interpretation

This study represents the first report of novel heterozygous SLC5A6 mutations in patients with axonal CMT and SMVTD, expanding the phenotypic spectrum associated with SLC5A6 mutations. Notably, we observed significant therapeutic effects from multivitamin treatment in a patient.