We describe a sibling pair displaying an early infantile-onset, progressive neurodegenerative phenotype, with symptoms of developmental delay and epileptic encephalopathy developing from 12 to 14 months of age. Using whole exome sequencing, compound heterozygous variants were identified in SLC5A6, which encodes the sodium-dependent multivitamin transporter (SMVT) protein. SMVT is an important transporter of the B-group vitamins biotin, pantothenate, and lipoate. The protein is ubiquitously expressed and has major roles in vitamin uptake in the digestive system, as well as transport of these vitamins across the blood–brain barrier. Pathogenicity of the identified variants was demonstrated by impaired biotin uptake of mutant SMVT. Identification of this vitamin transporter as the genetic basis of this disorder guided targeted therapeutic intervention, resulting clinically in improvement of the patient’s neurocognitive and neuromotor function. This is the second report of biallelic mutations in SLC5A6 leading to a neurodegenerative disorder due to impaired biotin, pantothenate and lipoate uptake. The genetic and phenotypic overlap of these cases confirms mutations in SLC5A6 as the genetic cause of this disease phenotype. Recognition of the genetic disorder caused by SLC5A6 mutations is essential for early diagnosis and to facilitate timely intervention by triple vitamin (biotin, pantothenate, and lipoate) replacement therapy.

我们描述了一个兄弟姐妹对，表现出早期的婴儿发作，进行性神经退行性表型，伴有发育迟缓和癫痫性脑病的症状，年龄从12到14个月不等。使用整个外显子组测序，在SLC5A6中鉴定了复合杂合变体，它编码钠依赖性多种维生素转运蛋白（SMVT）。SMVT是B组维生素生物素，泛酸和硫辛酸的重要转运蛋白。该蛋白质无处不在，在消化系统中维生素的吸收以及这些维生素跨血脑屏障的运输中起着重要作用。突变SMVT的生物素摄取受损证明了已鉴定变异的致病性。将该维生素转运蛋白鉴定为该疾病的遗传基础可指导有针对性的治疗干预，从而在临床上改善了患者的神经认知和神经运动功能。这是SLC5A6中双等位基因突变的第二份报告由于生物素，泛酸和硫辛酸酯的吸收受损而导致神经退行性疾病。这些病例的遗传和表型重叠证实了SLC5A6中的突变是该疾病表型的遗传原因。认识到由SLC5A6突变引起的遗传疾病对于早期诊断和促进及时采用三联维生素（生物素，泛酸和硫辛酸）替代疗法进行干预至关重要。