Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disorder of fatty acid metabolism (MIM 201450), caused by a deficiency of the MCAD enzyme. Tandem mass spectrometry of organic acids in urine, and carnitines in blood spots, allows the diagnosis to be unequivocally determined due to the accumulation of specific undegraded compounds. MCAD deficiency has an incidence in the UK of between 1/6500 and 1/20000 live births. It is clinically heterogeneous but often presents as an episodic disease resembling Reye syndrome, with vomiting, lethargy and coma after metabolic stress, prolonged fasting or infection. Patients may also have cardiomyopathy and/or skeletal myopathy, and some patients present as sudden infant death cases. Between episodes patients can appear normal and biochemical abnormalities can be absent. The gene encoding the MCAD enzyme (ACADM) is located at 1p31 and the mutation c.985A>G causes the replacement of the amino acid lysine with glutamic acid at codon 329 (p.Lys329Glu). This causes loss of MCAD activity and accounts for approximately 90% of mutant alleles.
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When requesting this test please use the referral form provided. Please also refer to any additional information provided for this test.
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Clinically affected patients should have their diagnosis confirmed by biochemical analysis. Affected patients can then be referred for mutation testing. If the necessary patient samples are unavailable genetic testing can be undertaken in the parents of an affected child. Level 1 Mutation Analysis: Testing for the common c.985A>G mutation by PCR and restriction enzyme digest.
Level 2 Mutation Analysis: Direct sequencing of exons 1 to 12 of the ACADM gene in 11 fragments.
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Great Ormond Street Hospital NE Thames Regional Genetics Service Laboratories
Great Ormond Street Hospital for Children
37 Queen Square
1ml EDTA neonates, 5ml EDTA adults
Common mutation - 10 days; gene screen - 40 days
Disease / group
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Prenatals must be arranged in advance, through a Clinical Genetics department if possible. Amniotic fluid or CV samples should be sent to Cytogenetics for dissecting and culturing, with instructions to forward the sample to the Regional Molecular Genetics laboratory for analysis