This report describes SLC5A6-related disorders, a range of disorders resulting from an inability to effectively uptake biotin, pantothenic acid, and lipoic acid. These disorders include peripheral motor neuropathy, childhood-onset, biotin-responsive (COMNB; MIM:619903), sodium-dependent multivitamin transporter deficiency (SMVTD; MIM:618973), and a potential new disorder, spontaneously remitting developmental delay with brain cysts' (SRDDBC), which is phenotypically intermediate between COMNB and SMVTD. The gene implicated is SLC5A6, which encodes the sodium-dependent multivitamin transporter. There are two high-scoring fly orthologs, Dmel\CG10444 and CG32669, as well as several moderately-scoring orthologs paralogous to those two genes. Only Dmel\CG10444 has been analyzed in the context of a human disease model, and amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated have been generated for this gene. Additionally, a construct reflecting a variant implicated in disease, Dmel\CG10444;p.S56F (orthologous to Hsap\SLC5A6;p.S74F, a variant associated with SRDDBC) has been generated. See the 'Disease-Implicated Variants' table below.
UAS constructs of the wild-type human Hsap\SLC5A6 gene have been introduced into flies, but have not been characterized in the context of this disease model.
Homozygous amorphic alleles of Dmel\CG10444 are lethal. Lethality can be rescued by overexpression of wild-type Dmel\CG10444, but not by either wild-type Hsap\SLC5A6, or by a construct of Dmel\CG10444 bearing a disease-implicated variant (FBrf0258598).
[updated Apr. 2024 by FlyBase; FBrf0222196]
SLC5A6-related disorders range from peripheral motor neuropathy, childhood-onset, biotin-responsive (COMNB; MIM:619903) to sodium-dependent multivitamin transporter deficiency (SMVTD; MIM:618973). COMNB symptoms are limited largely to peripheral motor neuropathy, presenting at around 10 years of age. SMVTD presents with symptoms affecting multiple organs and can include gastrointestinal hemorrhage, brain atrophy, and global developmental delay, at birth or in infancy, and can be fatal if untreated. Both disorders can be treated with replacement therapy of the nutrients biotin, pantothenic acid, and lipoic acid. A potential disorder, with phenotypic severity between COMNB and SMVTD has been identified and tentatively named 'spontaneously remitting developmental delay with brain cysts' (SRDDBC) (Utsuno, et al., 2024, pubmed:38012394; FBrf0258598).
The diseases associated with SLC5A6 exhibit autosomal recessive or compound heterozygous patterns of inheritance. [from MIM:619903 and MIM:618973, 2024.02.20]
The SLC5A6 gene encodes a transmembrane protein that is responsible for the transport of the water-soluble vitamins biotin and pantothenic acid and the metabolite lipoate in both the digestive system and across the blood-brain barrier (summary by Sabui et al. pubmed:29669219, 2018 and Byrne et al., 2019 pubmed:31754459). [from MIM:604024; 2024.02.20]
High-scoring ortholog of human SLCA56, SLC5A8, SLC5A12, and SLC5A5 (many Drosophila to many human).
High-scoring ortholog of human SLCA56, SLC5A12, SLC5A8, and SLC5A5 (many Drosophila to many human).
