A New Case of Sodium-dependent Multivitamin Transporter Defect Occurring As a Life-threatening Condition Responsive to Early Vitamin Supplementation and Literature Review

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2024 Feb 26

PMID 38407570

Authors

F-X Van Vyve

N Mercier

J Papadopoulos

C Heijmans

H Dessy

O Monestier

J P Dewulf

D Roland

Affiliations

Soon will be listed here.

Abstract

Background: Biallelic pathogenic variants in SLC5A6 resulting in sodium-dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin-responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms.

Methods: We describe a case report of a 5-month-old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium-dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation).

Results: We highlight the life-threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3-hydroxyisovaleric acid (3-HIA) as previously reported in this disease in literature.

Conclusion: SMVT deficiency is a vitamin-responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3-hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life-threatening.

Citing Articles

Rare Diseases Linked to Mutations in Vitamin Transporters Expressed in the Human Blood-Brain Barrier.

Yee S, Wang J, Giacomini K Clin Pharmacol Ther. 2024; 116(6):1513-1520.

PMID: 39234898 PMC: 11567784. DOI: 10.1002/cpt.3433.

A new case of sodium-dependent multivitamin transporter defect occurring as a life-threatening condition responsive to early vitamin supplementation and literature review.

Van Vyve F, Mercier N, Papadopoulos J, Heijmans C, Dessy H, Monestier O Mol Genet Genomic Med. 2024; 12(2):e2388.

PMID: 38407570 PMC: 10847706. DOI: 10.1002/mgg3.2388.

References

Mock D, Stratton S, Horvath T, Bogusiewicz A, Matthews N, Henrich C . Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans. J Nutr. 2011; 141(11):1925-30. PMC: 3192457. DOI: 10.3945/jn.111.146126. View

Rupasinghe K, Onyeador N . Sodium-dependent multivitamin transporter defects: a rare cause of recurrent vomiting and faltering growth. Frontline Gastroenterol. 2023; 14(4):346-349. PMC: 11138166. DOI: 10.1136/flgastro-2022-102344. View

Subramanian V, Constantinescu A, Benke P, Said H . Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. Hum Genet. 2016; 136(2):253-261. PMC: 5263180. DOI: 10.1007/s00439-016-1751-x. View

Hauth I, Waterham H, Wanders R, van der Crabben S, van Karnebeek C . A mild case of sodium-dependent multivitamin transporter (SMVT) deficiency illustrating the importance of treatment response in variant classification. Cold Spring Harb Mol Case Stud. 2022; 8(2). PMC: 8958925. DOI: 10.1101/mcs.a006185. View

Said H . Intestinal absorption of water-soluble vitamins in health and disease. Biochem J. 2011; 437(3):357-72. PMC: 4049159. DOI: 10.1042/BJ20110326. View

Ghosal A, Lambrecht N, Subramanya S, Kapadia R, Said H . Conditional knockout of the Slc5a6 gene in mouse intestine impairs biotin absorption. Am J Physiol Gastrointest Liver Physiol. 2012; 304(1):G64-71. PMC: 3543636. DOI: 10.1152/ajpgi.00379.2012. View

Quick M, Shi L . The sodium/multivitamin transporter: a multipotent system with therapeutic implications. Vitam Horm. 2015; 98:63-100. PMC: 5530880. DOI: 10.1016/bs.vh.2014.12.003. View

Tankeu A, Van Winckel G, Elmers J, Jaccard E, Superti-Furga A, Wolf B . Biotinidase deficiency: What have we learned in forty years?. Mol Genet Metab. 2023; 138(4):107560. DOI: 10.1016/j.ymgme.2023.107560. View

Schwantje M, de Sain-van der Velden M, Jans J, Van Gassen K, Dorrepaal C, Koop K . Genetic defect of the sodium-dependent multivitamin transporter: A treatable disease, mimicking biotinidase deficiency. JIMD Rep. 2019; 48(1):11-14. PMC: 6606985. DOI: 10.1002/jmd2.12040. View

10.

Pacheco-Alvarez D, Solorzano-Vargas R, Gravel R, Cervantes-Roldan R, Velazquez A, Leon-Del-Rio A . Paradoxical regulation of biotin utilization in brain and liver and implications for inherited multiple carboxylase deficiency. J Biol Chem. 2004; 279(50):52312-8. DOI: 10.1074/jbc.M407056200. View

11.

Sabui S, Kapadia R, Ghosal A, Schneider M, Lambrecht N, Said H . Biotin and pantothenic acid oversupplementation to conditional SLC5A6 KO mice prevents the development of intestinal mucosal abnormalities and growth defects. Am J Physiol Cell Physiol. 2018; 315(1):C73-C79. PMC: 6087731. DOI: 10.1152/ajpcell.00319.2017. View

12.

Montomoli M, Vetro A, Tubili F, Donati M, Daniotti M, Pochiero F . A novel SLC5A6 homozygous variant in a family with multivitamin-dependent neurometabolic disorder: Phenotype expansion and long-term follow-up. Eur J Med Genet. 2023; 66(8):104808. DOI: 10.1016/j.ejmg.2023.104808. View

13.

Hsieh C, Lee J, Sung H, Huang Y, Ding Y, Li C . Novel SLC5A6 mutations lead to B lymphocyte maturation defects with metabolic abnormality rescuable by biotin replenishment. Clin Immunol. 2023; 257:109855. DOI: 10.1016/j.clim.2023.109855. View

14.

Uchida Y, Ito K, Ohtsuki S, Kubo Y, Suzuki T, Terasaki T . Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. J Neurochem. 2015; 134(1):97-112. DOI: 10.1111/jnc.13092. View

15.

Holling T, Nampoothiri S, Tarhan B, Schneeberger P, Vinayan K, Yesodharan D . Novel biallelic variants expand the SLC5A6-related phenotypic spectrum. Eur J Hum Genet. 2022; 30(4):439-449. PMC: 8747999. DOI: 10.1038/s41431-021-01033-2. View

16.

Said H . Biotin: biochemical, physiological and clinical aspects. Subcell Biochem. 2011; 56:1-19. DOI: 10.1007/978-94-007-2199-9_1. View

17.

Van Vyve F, Mercier N, Papadopoulos J, Heijmans C, Dessy H, Monestier O . A new case of sodium-dependent multivitamin transporter defect occurring as a life-threatening condition responsive to early vitamin supplementation and literature review. Mol Genet Genomic Med. 2024; 12(2):e2388. PMC: 10847706. DOI: 10.1002/mgg3.2388. View

18.

Velazquez-Arellano A, de la Luz Hernandez-Esquivel M, Sanchez R, Ortega-Cuellar D, Rodriguez-Fuentes N, Cano S . Functional and metabolic implications of biotin deficiency for the rat heart. Mol Genet Metab. 2008; 95(4):213-9. DOI: 10.1016/j.ymgme.2008.08.002. View

19.

Byrne A, Arts P, Polyak S, Feng J, Schreiber A, Kassahn K . Identification and targeted management of a neurodegenerative disorder caused by biallelic mutations in SLC5A6. NPJ Genom Med. 2019; 4:28. PMC: 6856110. DOI: 10.1038/s41525-019-0103-x. View