Version 4.5 (October 2011)
NE THAMES REGIONAL MOLECULAR GENETICS SERVICE
Long chain acyl-CoA dehydrogenase (LCHAD) deficiency
Contact details Introduction Long chain acyl-CoA dehydrogenase (LCHAD) deficiency is an autosomal Molecular Genetics recessive disorder of fatty acid metabolism (MIM 201460), caused by a GOSH NHS Trust Level 6 deficiency of the long-chain hydroxyacyl-CoA dehydrogenase (HADHA) York House enzyme. Tandem mass spectrometry of organic acids in urine, and carnitines 37 Queen Square in blood spots, allows the diagnosis to be unequivocally determined due to the London accumulation of specific undegraded compounds. WC1N 3BH LCHAD deficiency is clinically heterogeneous but is often characterised by cardiomyopathy, skeletal myopathy, hypoglycemia, pigmentary retinopathy or Telephone +44 (0) 20 7762 6888 sudden infant death. An additional clinical complication can occur in the Fax pregnant mothers of affected fetuses; they may experience maternal acute +44 (0) 20 7813 8196 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.
Samples required Referrals
5ml venous blood in • Clinically affected patients should have their diagnosis confirmed by plastic EDTA bottles biochemical analysis. Affected patients can then be referred for (>1ml from neonates) mutation testing. If the necessary patient samples are unavailable genetic testing can be undertaken in the parents of an affected child. Prenatals must be • Pregnant patients who have AFLP can be referred for carrier testing, arranged in advance, along with their partners. through a Clinical • Carrier testing can be offered to the adult relatives of affected patients Genetics department if possible. Amniotic fluid once a disease causing mutation has been identified and partner or CV samples should testing is offered to confirmed carriers. be sent to Cytogenetics for Prenatal testing dissecting and Prenatal testing, by genetic analysis, is available to couples that have both culturing, with previously been shown to be carriers of the common mutation. Prenatal instructions to forward diagnosis is also offered by biochemistry regardless of mutation. Please the sample to the contact the laboratory to discuss. Regional Molecular
Genetics laboratory for analysis Service offered Testing for the presence of the common c.1528G>C mutation (p.Glu510Gln) in A completed DNA the HADHA gene by PCR & restriction enzyme digest. Screening of the request card should remainder of the gene is not available. accompany all samples. Target reporting time Routine analysis - 2 weeks. For urgent samples please contact the laboratory.
Contact details for Biochemistry/ Enzyme Unit: Enzyme Unit, Chemical Pathology, Great Ormond Street Hospital, London, WC1N 3JH Tel: +44 (0) 20 7405 9200 (x2509)
Patient details To facilitate accurate testing and reporting please provide patient demographic details (full name, date of birth, address and ethnic origin), details of any relevant family history and full contact details for the referring clinician