Biallelic pathogenic variants in SLC5A6 gene, resulting in sodium-dependent multivitamin transporter (SMVT) defect, is a recently described inborn error of metabolism mimicking biotinidase deficiency. SMVT is a transmembrane protein expressed in multiple tissues including, kidney, liver, heart and brain. SMVT plays a key role in water-soluble vitamins biotin and pantothenic acid as well as α-lipoic acid intestinal absorption, regulating their cellular uptake and transport across the blood-brain barrier. Biotin is a known cofactor of carboxylases involved in various metabolic reactions including fatty acid synthesis, gluconeogenesis and lipid and branched-chain amino acid (BCAA) catabolism. Pantothenic acid is a coenzyme A precursor involved, for example, in glycolysis, Krebs cycle, fatty acid oxidation and BCAA catabolism. α–lipoic acid is a cofactor of several enzymes of the intermediary metabolism and has antioxidative and anti-inflammatory effects. Only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairment (neurodevelopmental delay, microcephaly but also thin corpus callosum), gastro-intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis with hypoglycemia and recently optic nerves atrophy. Only four patients have been reported to have cardiac involvement. We report a new presentation of SMVT defect in a 5-month-old girl. Familial history was marked by consanguinity and the unexplained death of a brother at the age of 8 months after a flu. Patient had normal parameters at birth and a normal psychomotor development but microcephaly and failure to thrive. She was initially admitted for neurological distress, hemodynamic shock, ketoacidosis and lactic acidosis (pH 7.33, BE -5 mmol/L, lactate 6 mmol/L) associated with a refusal to eat and without hypoglycemia. She was quickly transferred to the pediatric intensive care unit (PICU) for invasive ventilation, inotropic support and intravenous saline and glucose infusion. Heart failure with a reduced left ventricular ejection fraction (LVEF) 32% (N > 60%) was rapidly identified. After two weeks of cardiac support, the baby was discharged with a complete normalisation of cardiac function. Two weeks later, she relapsed with a refusal to eat and vomiting. She was promptly readmitted to the PICU with severe metabolic acidosis (pH 7.1, base excess -16.1 mmol/L), hyperlactatemia up to 8.8 mmol/L and a severe haemodynamic shock associated with severe cardiac dysfunction (LVEF 17%, elevated troponin and NT-pro-BNP). A rapid normalisation of lactic acidosis was observed with saline and glucose (up to 10mg/kg/min) infusion, L-carnitine 100mg/kg and a multivitamin cocktail (B1 100mg, B2 1mg, biotin 10mg and B12 50mg) supplementation. Due to feeding problems and chronic diarrhea, she developed poor weight gain and required temporary nasogastric tube feeding. Later, the patient developed persistent severe refractory cardiac dysfunction despite cardiotonics and diuretics. Rapid trio WES identified a homozygous potentially pathogenic missense variant in SLC5A6 gene (NM_021095.4): c.1310C>T p.(Pro437Leu). Under treatment with biotine 15 mg and pantothenic acid 100 mg we observed an improvement in neurodevelopment, gradual enteral refeeding and an impressive and complete cardiac function recovery with normalization at 3-months follow-up. Biallelic pathogenic variants in SLC5A6 are responsible for the sodium-dependent multivitamin transporter (SMVT) defect, a recently described inborn error of metabolism. The presence of elevated 3-hydroxyisovaleric acid on urinary organic acid chromatography may indicate a defect in the symporter of biotin, pantothenic acid and α-lipoic acid in the absence of biotinidase deficiency. Rapid sequencing of the whole exome allowed for an accurate diagnosis and further a highly effective treatment. In parallel to recently and only one case published with cardiac recovery, our patient presented with severe cardiac decompensation that was successfully treated with biotin and pantothenic acid and normalisation of cardiac function on water soluble vitamins supplementation.