Riboflavin responsive mitochondrial myopathy is a new phenotype of dihydrolipoamide dehydrogenase deficiency. The chaperon-like effect of vitamin B2

• DOI: 10.1016/j.mito.2014.09.006
• Publication Date: 2014-09-22T01:30:18Z
• Authors: Rosalba Carrozzo; Alessandra Torraco; Giuseppe Fiermonte; Diego Martinelli; Michela Di Nottia; Teresa Rizza; Angelo Vozza; Daniela Verrigni; Daria Diodato; Giovanni Parisi; Arianna Maiorana; Cristiano Rizzo; Ciro Leonardo Pierri; Stefania Zucano; Fiorella Piemonte; Enrico Bertini; Carlo Dionisi-Vici
• Keywords: Male; 0303 health sciences; Protein Stability; Biopsy; Muscles; Riboflavin; Gene Expression; Mitochondrial Myopathies; Young Adult; 03 medical and health sciences; Phenotype; Maple Syrup Urine Disease; Vitamin B Complex; Humans; Acidosis, Lactic

Dihydrolipoamide dehydrogenase (DLD, E3) is a flavoprotein common to pyruvate, α-ketoglutarate and branched-chain α-keto acid dehydrogenases. We found two novel DLD mutations (p.I40Lfs*4; p.G461E) in a 19 year-old patient with lactic acidosis and a complex amino- and organic aciduria consistent with DLD deficiency, manifesting progressive exertional fatigue. Muscle biopsy showed mitochondrial proliferation and lack of DLD cross-reacting material. Riboflavin supplementation determined the complete resolution of exercise intolerance with the partial restoration of the DLD protein and disappearance of mitochondrial proliferation in the muscle. Morphological and functional studies support the riboflavin chaperon-like role in stabilizing DLD protein with rescue of its expression in the muscle.