Long chain acyl-CoA dehydrogenase (LCHAD) deficiency is an autosomal recessive disorder of fatty acid metabolism (MIM 201460), caused by a deficiency of the long-chain hydroxyacyl-CoA dehydrogenase (HADHA) 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. LCHAD deficiency is clinically heterogeneous but is often characterised by cardiomyopathy, skeletal myopathy, hypoglycemia, pigmentary retinopathy or sudden infant death. An additional clinical complication can occur in the pregnant mothers of affected fetuses; they may experience maternal acute fatty liver of pregnancy (AFLP) syndrome or hypertension/haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. The gene encoding the HADHA enzyme is located at 2p23. The mutation, c.1528G>C, causes the replacement of the amino acid glutamic acid with glutamine at codon 510 (p.Glu510Gln), this results in loss of LCHAD activity and accounts for approximately 87% of mutant alleles.
Request a test
When requesting this test please use the referral form provided. Please also refer to any additional information provided for this test.
Download the referral form >
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. Pregnant patients who have AFLP can be referred for carrier testing, along with their partners. Testing for the presence of the common c.1528G>C mutation (p.Glu510Gln) in the HADHA gene by PCR & restriction enzyme digest. Screening of the remainder of the gene is not available.
Download additional information >
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
Disease / group
Call in advance?
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