Riboflavin‐responsive lipid‐storage myopathy and glutaric aciduria type II of early adult onset

Abstract

A 17-year-old girl with progressive lipid-storage myopathy for 2 years had low muscle carnitine levels. There was no therapeutic response to prednisone and DL-carnitine-HCl. Chemical findings indicated glutaric aciduria type II. Riboflavin therapy and a fat-restricted, carbohydrate-enriched diet resulted in dramatic improvement. Low carnitine concentrations in plasma and muscle were observed in three asymptomatic sisters who had normal urinary excretion patterns. There was impaired mitochondrial beta-oxidation in cultured skin fibroblasts from the index patient and all three siblings.

Lipid Storage Myopathy in Multiple Acyl-CoA Dehydrogenase Deficiency: An Adult Case

“…This may also explain the amelioration of the clinical and pathological picture after reduced lipid di etary intake. Improvement after low-lipid diet has alreadybeen reported in MAAD [ 12], in other defects of p-oxidation [39] and in cases of lipid storage myopathy in which P-oxydation was not assayed [40], As in other reported cases, we detected in our patient low levels of muscle and liver carnitine [1][2][3][4][5][6][7]10] and increased CPT activity [1.5, 7], Mitochondrial abnormal ities, such as those we observed, have also been reported [6] and interpreted as a result of p-oxidation defects. In our case, this explanation is indirectly supported by the absence of mitochondrial DNA alterations, frequently observed in primary mitochondrial diseases [25.…”

“…MADD is a severe metabolic disorder which may mani fest itself in utcro [27], but usually does so in early infancy [28][29][30][31][32][33][34][35], The clinical picture is characterized by vomiting, hypoglycemia, acidosis and fatal outcome: muscle in volvement has been documented in only 1 case [36], but hypotonia is reported by many authors [27.29-31,33. 35, 37], In older patients, MADD is less frequently reported [1][2][3][4][5][6][7][10][11][12][13], and its expression is more heterogeneous (table 7). MADD has been directly demonstrated in skele tal muscle in some cases [5,6] and deduced from organic aciduria and impaired oxidation in vitro in others [1.4, 10.…”

“…Different defects of acyl-CoA dehydrogenases associated with secondary carnitine defi ciency have been identified [1,2,4,5,7,8], The clinical picture ranges from cases with neonatal onset and rapidly fatal outcome, usually classified as glutaric aciduria type II [9], to juvenile or adult cases [1][2][3][4][5][6][7][10][11][12][13]; these are much less frequent and present heterogeneous clinical and biochemical features.…”

Therapy of mitochondrial disorders

“…It is however effective in multiple carboxylase deficiency either due to holocarboxylase synthetase or biotinidase deficiency. Riboflavin, vitamin B2, precursor of flavin monophosphate and flavin adenine dinucleotide, which are part of NADH-coenzyme Q reductase and of complex II and many acyl-CoA dehydrogenases, has proved effective in some cases of multiple acyl-CoA dehydrogenase deficiency (Gregersen, 1985;de Visser et al, 1986), alone or in combination with carnitine, and in cases of NADH-coenzyme Q reductase deficiency myopathy (Arts et al, 1983). This effect might also be due to positive regulation of flavin-containing enzyme protein production in the presence of riboflavin, FMN and FAD, respectively.…”

Newborn Screening for Glutaric Aciduria-II: The New England Experience

“…The underlying etiology is a functional deficiency of the electron transport flavoprotein (ETF, comprised of the alpha and beta subunits; ETFA, ETFB 130410) or electron transfer flavoprotein dehydrogenase (ETF-DH; EC 1.5.5.1), caused by mutations in any one of the ETFA, ETFB, or ETFDH genes (Goodman et al 2002;Olsen et al 2007). GA-II can present as either a severe neonatal form with or without congenital anomalies, or as a milder late-onset disease (Al-Essa et al 2000;Bohm et al 1982;Curcoy et al 2003;de Visser et al 1986;Loehr et al 1990;Rhead et al 1987). Individuals with the severe neonatal form usually present within 24-48 h after birth with severe metabolic abnormalities (nonketotic hypoglycemia, metabolic acidosis, hyperammonemia, lactic acidosis), hypotonia, hepatomegaly, and cardiomegaly, and have a rapidly fatal course.…”