Riboflavin therapy - Biochemical heterogeneity in two adult lipid storage myopathies

Two unrelated adult males, aged 36 (patient 1) and 25 (patient 2) years, pr esented with subacute carnitine-deficient lipid storage myopathy that was t otally and partly responsive to riboflavin supplementation in the two patie nts, respectively. Plasma acyl-carnitine and urinary organic acid profiles indicated multiple acyl coenzyme A dehydrogenase deficiency, which was mild in patient 1 and severe in patient 2, The activities of short-chain and me dium-chain acyl coenzyme A dehydrogenases in mitochondrial fractions were d ecreased, especially in patient 2, This was in agreement with Western blott ing results, Flavin-dependent complexes I and II were studied by immunoblot ting and densitometric quantification of two-dimensional electrophoresis wi th comparable results, Complex I was present in normal amounts in both pati ents, whereas complex II was decreased only in the pretherapy muscle of pat ient 2, Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) c oncentrations in muscle and isolated mitochondria, and the activity of mito chondrial FAD pyrophosphatase, showed that patient 1 had low levels of FAD (46%) and FMN (49%) in mitochondria, with a significant increase (P < 0.01) in mitochondrial FAD pyrophosphatase (273%) compared with controls. Patien t 2 had similar low levels of FAD and FMN in both total muscle (FAD and FMN 22% of controls) and mitochondria (FAD 26%; FMN 16%) and normal activity o f mitochondrial FAD pyrophosphatase, All of these biochemical parameters we re either totally or partly corrected after riboflavin therapy.