Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Summary: We report a patient with lipid-storage myopathy due to multiple acyl-CoA dehydrogenation deficiency (MADD). Molecular genetic analysis showed that she was compound heterozygous for mutations in the gene for electron transfer flavoprotein:ubiquinone oxidoreductase (ETFQO). Despite a good initial response to treatment, she developed respiratory insufficiency at age 14 years and has required long-term overnight ventilation. Thus, MADD is one of the few conditions that can cause a myopathy with weakness of the respiratory muscles out of proportion to the limb muscles.
- Antozzi C, Garavaglia B, Mora M, et al (1994) Late-onset riboflavin-responsive myopathy with combined multiple acyl-coenzyme A dehydrogenase and respiratory chain deficiency. Neurology 44: 2153–2158.
- Beard SE, Goodman SI, Bemelen K, et al (1995) Characterization of a mutation that abolishes quinone reduction by electron transfer flavoprotein-ubiquinone oxidoreductase. Hum Mol Genet 4: 157–161.
- Bell RB, Brownell AK, Roe CR, et al (1990) Electron transfer flavoprotein: ubiquinone oxidoreductase (ETF:QO) deficiency in an adult. Neurology 40: 1779–1782.
- Bradley WG, Hudgson P, Gardner-Medwin D, et al (1969) Myopathy associated with abnormal lipid metabolism in skeletal muscle. Lancet 1: 495–498.
- Colombo I, Finocchiaro G, Garavaglia B, et al (1994) Mutations and polymorphisms of the gene encoding the beta-subunit of the electron transfer flavoprotein in three patients with glutaric acidemia type II. Hum Mol Genet 3: 429–435.
- Curcoy A, Olsen RK, Ribes A et al (2003) Late-onset form of beta-electron transfer flavoprotein deficiency. Mol Genet Metab 78: 247–249.
- Cwik VA (2000) Disorders of lipid metabolism in skeletal muscle. Neurol Clin 18: 167–184.
- de Visser M, Scholte HR, Schutgens RB, et al (1986) Riboflavin-responsive lipid-storage myopathy and glutaric aciduria type II of early adult onset. Neurology 36: 367–372.
- DiDonato S, Frerman FE, Rimoldi M, et al (1986) Systemic carnitine deficiency due to lack of electron transfer flavoprotein:ubiquinone oxidoreductase. Neurology 36: 957–963.
- DiDonato S. Gellera C, Peluchetti D, et al (1989) Normalization of short-chain acylcoenzyme A dehydrogenase after riboflavin treatment in a girl with multiple acylcoenzyme A dehydrogenase-deficient myopathy. Ann Neurol 25: 479–484.
- Finocchiaro G, Ito M, Ikeda Y, et al (1988) Molecular cloning and nucleotide sequence of cDNAs encoding the alpha-subunit of human electron transfer flavoprotein. J Biol Chem 263: 15773–15780.
- Finocchiaro G, Colombo I, Garavaglia B, et al (1993) cDNA cloning and mitochondrial import of the beta-subunit of the human electron-transfer flavoprotein, Eur J Biochem 213: 1003–1008.
- Freneaux E, Sheffield VC, Molin L, et al (1992) Glutaric acidemia type II. Heterogeneity in beta-oxidation flux, polypeptide synthesis, and complementary DNA mutations in the alpha subunit of electron transfer flavoprotein in eight patients. J Clin I nvest 90: 1679–1686.
- Frerman FE, Goodman SI (2001). Defects of electron transfer flavoprotein and electron transfer flavoprotein:ubiquinone oxidoreductase: glutaric aciduria type II. In Scriver CR, Beaudet AL, Sly WS, Valle, D, eds; Childs B, Kinzler KW, Vogelstein B, assoc. eds. TheMetabolic andMolecular Bases of InheritedDisease, 8th edn. New York: McGraw-Hill, 2357–2365.
- Frischmeyer PA, Dietz HC (1999) Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet 8: 1893–1900.
- Goodman SI, Axtell KM, Bindoff LA, et al (1994) Molecular cloning and expression of a cDNA encoding human electron transfer flavoprotein-ubiquinone oxidoreductase. Eur J Biochem 219: 277–286.
- Goodman SI, Binard R, Woontner M, et al (2002) Glutaric acidemia type II: gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene.Mol Genet Metab 77: 86–90.
- Howard RS, Wiles CM, Hirsch NP, et al (1993) Respiratory involvement in primary muscle disorders: assessment and management. Q J Med 86: 175–189.
- Indo Y, Glassberg R, Yokota I, et al (1991) Molecular characterization of variant alpha-subunit of electron transfer flavoprotein in three patients with glutaric acidemia type II and identi-fication of glycine substitution for valine-157 in the sequence of the precursor, producing an unstable mature protein in a patient. Am J hum Genet 49: 575–580.
- Loehr JP, Goodman SI, Frerman FE (1990) Glutaric acidemia type II: heterogeneity of clinical and biochemical phenotypes. Pediatr Res 27: 311–315.
- Manning NJ, Olpin SE, Pollitt RJ, et al (1990) A comparison of [9,10-3H]palmitic and [9,10-3H]myristic acids for the detection of defects of fatty acid oxidation in intact cultured fibroblasts. J I nherit Metab Dis 13: 58–68.
- Mellies U, Ragette R, Schwake C, et al (2001) Sleep-disordered breathing and respiratory failure in acid maltase deficiency. Neurology 57: 1290–1295.
- Mongini T, Doriguzzi C, Palmucci L, et al (1992) Lipid storage myopathy in multiple acyl-CoA dehydrogenase deficiency: an adult case. Eur Neurol 32: 170–176.
- Olpin SE, Manning NJ, Pollitt RJ, et al (1997) Improved detection of long-chain fatty acid oxidation defects in intact cells using [9,10-3H]oleic acid. J I nheritMetab Dis 20: 415–419.
- Olsen RK, Andresen BS, Christensen E, et al (2003) Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat 22: 12–23.
- Purevjav E, Kimura M, Takusa Y, et al (2002) Molecular study of electron transfer flavoprotein alpha-subunit deficiency in two Japanese children with different phenotypes of glutaric acidemia type II. Eur J Clin Invest 32: 707–712.
- Rhead W, Roettger V, Marshall T, et al (1993) Multiple acyl-coenzyme A dehydrogenation disorder responsive to riboflavin: substrate oxidation, flavin metabolism, and flavoenzyme activities in fibroblasts. Pediatr Res 33: 129–135.
- Turnbull DM, Bartlett K, Eyre JA, et al (1998) Lipid storage myopathy due to glutaric aciduria type II: treatment of a potentially fatal myopathy. Dev Med Child Neurol 30: 667–672.
- Vergani L, Barile M, Angelini C, et al (1999) Riboflavin therapy. Biochemical heterogeneity in two adult lipid storage myopathies. Brain 122: 2401–2411.
- Yamaguchi S, Orii T, Suzuki Y, et al (1991) Newly identified forms of electron transfer flavoprotein deficiency in two patients with glutaric aciduria type II. Pediatr Res 29: 60–63.
- Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency
Journal of Inherited Metabolic Disease
Volume 27, Issue 5 , pp 671-678
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers
- Additional Links
- Industry Sectors
- Author Affiliations
- 1. Research Unit for Molecular Medicine, Aarhus University Hospital and Faculty of Health Sciences, Aarhus, Denmark
- 2. Department of Child Health, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
- 3. Research Unit for Molecular Medicine, Skejby Sygehus, Aarhus University Hospital, DK-8200, Aarhus N, Denmark. E-mail
- 4. Paediatric Department, North Tees General Hospital, Stockton, UK
- 5. Institute of Human Genetics, Aarhus University, Aarhus, Denmark
- 6. Chemical Pathology/Neonatal Screening and Metabolic Disease Service, Sheffield Children's Hospital, Sheffield, UK