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.

Keywords: SLC5A6; Korean; axonal sensorimotor polyneuropathy; multivitamin treatment; sodium‐dependent multivitamin transporter deficiency (SMVTD); therapeutic effect.

© 2025 Peripheral Nerve Society.

背景和目的： SLC5A6基因编码一种负责转运生物素、泛酸和硫辛酸的跨膜蛋白。SLC5A6基因突变表现出广泛的临床表型，如钠依赖性多种维生素转运蛋白缺乏症（SMVTD）、儿童期起病的生物素反应性周围运动神经病变（COMNB）以及混合轴索性和脱髓鞘感觉运动神经病变。本研究旨在识别韩国CMT患者群体中的致病性SLC5A6基因突变。

方法： 本研究对两名患有早发性轴索型感觉运动多发性神经病变和SMVTD的独立患者进行了全外显子测序，以确定遗传原因。我们还检查了SLC5A6基因突变患者的多种维生素补充疗法的效果。

结果： 我们在两名患者中发现了复合杂合变异（患者1：p.Arg94X 和 p.Phe522Ser；患者2：p.Cys443Tyr 和 p.Phe513_Lys515delinsLeu）。在患者2中，口服包括生物素、硫辛酸和泛酸在内的维生素补充方案显示出显著的治疗效果，包括停止周期性呕吐、手指皮肤病变的消退以及上肢和下肢肌无力的改善。

解释： 本研究是首次报告了在轴索型CMT患者中发现新的杂合突变SLC5A6基因，扩展了与SLC5A6基因突变相关的表型范围。值得注意的是，在一名患者的多种维生素治疗中观察到了显著的疗效。

关键词： SLC5A6；韩国；轴索感觉运动多发性神经病变；多种维生素治疗；钠依赖性多种维生素转运蛋白缺乏症（SMVTD）；治疗效果。