Fatty Acid Oxidation Disorders

Print Version
Disease Name Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Alternate name(s) N/A
Disease Classification Fatty Acid Oxidation Disorder
Variants Yes
Variant name

Mitochondrial trifunctional protein deficiency

Symptom onset Neonatal, infancy

Hypoketotic hypoglycemia, hypotonia, cardiomyopathy, hepatic disease, peripheral neuropathy and pigmentary retinopathy, rhabdomyolysis, sudden death

Natural history without treatment Possible developmental delay due to damage from hypoglycemic episodes, possible death due to cardiomyopathy or hepatic failure.
Natural history with treatment Intelligence is usually normal if there is no damage due to hypoglycemic crisis. Peripheral neuropathy, if present, may not improve with treatment.
Treatment Avoidance of fasting, use of uncooked starch, MCT treatments, carnitine supplementation, DHA supplementation (may prevent retinopathy, but this has not been proven)
Other Maternal complications in pregnancy include acute fatty liver of pregnancy, HELLP syndrome, and pre-eclampsia
Physical phenotype Hypotonia, cardiomyopathy and possible retinal changes
Inheritance Autosomal recessive
General population incidence Rare
Ethnic differences Yes
Population Finnish
Ethnic incidence 1:240 carrier rate for common mutation G1528C in Finland
Enzyme location Inner mitochondrial membrane, liver, heart, fibroblasts
Enzyme Function Metabolizes long chain fatty acids (C-12 to C-16 in length)
Missing Enzyme Long-chain 3-hydroxyacyl-CoA dehydrogenase or mitochondrial trifunctional protein
Metabolite changes Increased 3-hydroxydicarboxylic acids in urine, increased saturated and unsaturated 3-hydroxy organic acids, possible elevated CPK during acute illness.
Gene HADHA and HADHB (alpha and beta subunits)
Gene location 2p23
DNA testing available Yes – mutation analysis
DNA testing detail Common mutation, G1528C, accounts for 87% of all mutant alleles in LCHAD deficiency; 70% of affected individuals will be homozygous for this mutation. There is no common mutation in trifunctional protein deficiency.
Prenatal testing Enzyme analysis, protein analysis and direct DNA (when applicable).
MS/MS Profile C18:OH, C16:1OH, C16OH
OMIM Link http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600890
Genetests Link www.genetests.org
Support Group

FOD Family Support Group

Save Babies through Screening Foundation

Genetic Alliance

  Print Version


THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content ("Content"), including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET. This project is supported by a grant from the Maternal and Child Health Bureau, Health Resources and Service Administration, Genetic Services Branch, MCH Project #:1H46 MC 00189-03 http://mchb.hrsa.gov