Diagnostic assessment and long-term follow-up of 13 patients with Very Long-Chain Acyl-Coenzyme A dehydrogenase (VLCAD) deficiency |
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| Authors: | Pascal Laforêt Cécile Acquaviva-Bourdain Odile Rigal Michèle Brivet Isabelle Penisson-Besnier Brigitte Chabrol Denys Chaigne Odile Boespflug-Tanguy Cécile Laroche Anne-Laure Bedat-Millet Anthony Behin Isabelle Delevaux Anne Lombès Brage S. Andresen Bruno Eymard Christine Vianey-Saban |
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| Affiliation: | 1. Metabolic Genetics, Victorian Clinical Genetic Services, Murdoch Children''s Research Institute, The Royal Children''s Hospital, Flemington Road, Parkville, Victoria, Melbourne 3052, Australia;2. Department of Nutrition and Food Services, Royal Children''s Hospital, Flemington Road, Parkville, Victoria, Melbourne 3052, Australia;3. Be Active Sleep Eat (BASE) Facility, Department of Nutrition and Dietetics, Monash University, Faculty of Medicine, Nursing and Health Sciences, Level 1, 264 Ferntree Gully Road, VIC 3168, Melbourne, Australia;4. Department of Paediatrics, University of Melbourne, Royal Children''s Hospital, Flemington Road, Parkville, Victoria, Melbourne 3052, Australia;1. Pediatrics, University of Washington, Seattle, WA, USA;2. Environmental and Occupational Health, University of Washington, Seattle, WA, USA;3. Pediatrics, Children''s Hospital of Orange County, Orange, CA, USA;4. Genomics Section, Hawai''i Department of Health, Honolulu, HI, USA;5. Pediatrics, University of California San Diego, La Jolla, CA, USA;6. Genetic Disease Screening Program, California Department of Public Health, Richmond, CA, USA;7. Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA;8. Northwest Regional Newborn Screening Program, Oregon State Public Health Laboratory, Hillsboro, OR, USA;9. Office of Newborn Screening, Washington State Department of Health, Shoreline, WA, USA;1. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2600 anexo, 90035-003, Porto Alegre, Brazil;2. Beatrix Children''s Hospital, Section of Metabolic Diseases, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands;3. Post-Graduation Program in Genetics and Molecular Biology, UFRGS, Bento Gonçalves 9500/43323M, PO Box 15053, Porto Alegre, Brazil;4. Postgraduate Program in Pediatrics and Adolescent Health, UFRGS, Ramiro Barcelos 2400, 90035-003, Porto Alegre, Brazil;5. Postgraduate Program in Collective Health, Health Unit, Universidade do Extremo Sul Catarinense, Universitária 1105, 88806-000 Criciúma, Brazil;6. Department of Pediatrics, Hospital de Clínicas de Porto Alegre, Ramiro Barcelos 2400, 90035-003 Porto Alegre, Brazil;7. Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, Brazil;8. Department of Genetics, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, 90035-003 Porto Alegre, Brazil |
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| Abstract: | Very Long-Chain Acyl-CoA dehydrogenase (VLCAD) deficiency is an inborn error of mitochondrial long-chain fatty acid oxidation (FAO) most often occurring in childhood with cardiac or liver involvement, but rhabdomyolysis attacks have also been reported in adults. We report in this study the clinical, biochemical and molecular studies in 13 adult patients from 10 different families with VLCAD deficiency. The enzyme defect was demonstrated in cultured skin fibroblasts or lymphocytes. All patients exhibited exercise intolerance and recurrent rhabdomyolysis episodes, which were generally triggered by strenuous exercise, fasting, cold or fever (mean age at onset: 10 years). Inaugural life-threatening general manifestations also occurred before the age of 3 years in four patients. Increased levels of long-chain acylcarnitines with tetradecenoylcarnitine (C14:1) as the most prominent species were observed in all patients. Muscle biopsies showed a mild lipidosis in four patients. For all patients but two, molecular analysis showed homozygous (4 patients) or compound heterozygous genotype (7 patients). For the two remaining patients, only one mutation in a heterozygous state was detected. This study confirms that VLCAD deficiency, although being less frequent than CPT II deficiency, should be systematically considered in the differential diagnosis of exercise-induced rhabdomyolysis. Measurement of fasting blood acylcarnitines by tandem mass spectrometry allows accurate biochemical diagnosis and should therefore be performed in all patients presenting with unexplained muscle exercise intolerance or rhabdomyolysis. |
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