A novel SLC5A6 homozygous variant in a family with multivitamin-dependent neurometabolic disorder: Phenotype expansion and long-term follow-up

• Published in: European journal of medical genetics 2023-08, Vol.66 (8), p.104808-104808, Article 104808
• Main Authors: Montomoli, Martino, Vetro, Annalisa, Tubili, Flavia, Donati, Maria Alice, Daniotti, Marta, Pochiero, Francesca, Rivieri, Francesca, Girlando, Salvatore, Guerrini, Renzo
• Format: Article
• Language: English
• Subjects: Biotin deficiency; Lipoate deficiency; Multivitamin transporter; Optic atrophy; Pantothenate deficiency; Targeted therapy
• ISSN: 1769-7212; 1878-0849
• DOI: 10.1016/j.ejmg.2023.104808

The sodium-dependent multivitamin transporter (hSMVT) encoded by the SLC5A6 gene is required for the intestinal absorption of biotin, pantothenic acid and lipoate, three micronutrients essential for normal growth and development. Systemic deficiency of these elements, either occurring from nutritional causes or genetic defects, is associated with neurological disorders, growth delay, skin and hair changes, metabolic and immunological abnormalities. A few patients with biallelic variants of SLC5A6 have been reported, exhibiting a spectrum of neurological and systemic clinical features with variable severity. We describe three patients from a single family carrying a homozygous p.(Leu566Valfs*33) variant of SLC5A6 disrupting the frame of the C-terminal portion of the hSMVT. In these patients, we documented a severe disorder featuring developmental delay, sensory polyneuropathy, optic atrophy, recurrent infections, and repeated episodes of intestinal pseudo-obstruction. Two patients who did not receive multivitamin supplementation therapy died in early infancy. In a third patient, early supplementation of biotin and pantothenic acid stabilized the clinical picture changing the course of the disease. These findings extend genotype-phenotype correlations and show how a timely and lifelong multivitamin treatment may be crucial to reduce the risk of life-threatening events in patients with pathogenic variants of the SLC5A6 gene.