Late-onset riboflavin-responsive myopathy with combined multiple acyl coenzyme A dehydrogenase and respiratory chain deficiency.
We studied the effect of riboflavin treatment on the clinical status and on the activities of beta-oxidation and respiratory chain enzymes in a 69-year-old patient with late-onset myopathy. Before treatment, she was very weak and wasted in the limbs and trunk muscles; also, she could not walk or attend to daily activities. Marked lipid storage was present in the muscle biopsy. The activities of short-chain acyl coenzyme A (acyl-CoA) dehydrogenase (SCAD), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in isolated muscle mitochondria were reduced to less than 10% of control values. This defect in fatty acid oxidation was associated with a marked deficiency of two flavin-dependent respiratory chain complexes: complex I activity was 20% and complex II activity was 25% of control values. By contrast, the activities of the nonflavin-dependent complex III and complex IV were normal. Western blot analysis of the patient's muscle mitochondrial extracts with antibodies raised against purified SCAD, MCAD, and the alpha- and beta-subunits of the electron transfer flavoprotein (ETF) showed absence of SCAD cross-reacting material (CRM), markedly decreased MCAD-CRM, and normal amounts of both alpha- and beta-ETF-CRM. After riboflavin treatment, the patient's clinical status dramatically improved and morphologic changes in muscle disappeared. SCAD activity increased to 55% of control values, whereas MCAD, LCAD, and complex I and complex II activities normalized. SCAD and MCAD immunoreactivity was restored to normal. On the basis of our experience and the data in the literature, we concluded that some lipid storage myopathies can show dramatic response to riboflavin.
Antozzi
C
C
Neuromuscular Research Center, Istituto Nazionale Neurologico C. Besta, Milan, Italy.
Garavaglia
B
B
Mora
M
M
Rimoldi
M
M
Morandi
L
L
Ursino
E
E
DiDonato
S
S
D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency*; D000368:Aged; D004579:Electron Transport; D042963:Electron Transport Complex II; D005260:Female; D006801:Humans; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology; D009097:Multienzyme Complexes / Q000172:deficiency*; D009135:Muscular Diseases / Q000188:drug therapy* / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency*; D010088:Oxidoreductases / Q000172:deficiency*; D012256:Riboflavin / Q000627:therapeutic use*; D013385:Succinate Dehydrogenase / Q000172:deficiency*
D009097:Multienzyme Complexes; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D013385:Succinate Dehydrogenase; D016660:NAD(P)H Dehydrogenase (Quinone); D012256:Riboflavin