LCHAD deficiency is inherited in an autosomal recessive pattern. Normally a person has two functional HADHA genes. In people with LCHAD deficiency, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with LCHAD deficiency typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of LCHAD deficiency do not typically have symptoms. However, a mother who is pregnant with a baby with LCHAD deficiency is at risk of illness during pregnancy. The mother may develop HELLP syndrome (haemolysis, elevated liver enzymes, low platelets) or AFLP (acute fatty liver of pregnancy).
The symptoms of LCHAD deficiency may begin anytime during infancy through early childhood. They are variable from one individual to the next but may include hypoglycemia (low blood sugar), liver problems, cardiomyopathy (disease of the heart muscle), retinopathy (disease of the eye) and hypotonia (low muscle tone). Later in childhood, rhabdomyolysis (muscle breakdown) and muscle pain may occur.
- Incidence: The overall incidence is unknown.
- New York State Method of Screening (First Tier): Screening for LCHAD deficiency is accomplished by measuring acylcarnitines (C16OH and C18:1OH) by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Screening may be normal in patients with mild LCHAD deficiency who were recently fed, received IV glucose or who were not ill when the specimen was collected. Newborn screening cannot distinguish between LCHAD and Trifunctional protein deficiency (TFP).
- Interpretation/reporting of data: Results are reported as screen negative or as a referral. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for LCHAD deficiency are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of LCHAD deficiency.
Diagnostic testing may include quantification of plasma acylcarnitines, molecular genetic testing of the HADHA gene and functional analysis of fatty acid oxidation on fibroblasts (skin cells).
Treatment is through dietary management, including avoidance of fasting, drinking low-fat formula and supplementation with medium-chain triglycerides (MCT) as a source of supplemental calories. Treatment for cardiac involvement or rhabdomyolysis is supportive. During times of illness, hospitalization may be required to monitor and treat hypoglycemia.
Prognosis is variable and dependent on multiple factors, including the severity of disease and response to treatments.
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a fatty acid oxidation disorder (inherited metabolic disorder).
LCHAD deficiency is caused by mutations in the HADHA gene. Individuals with this disorder are unable to convert certain fats to energy and may develop symptoms during times of high energy need such as fasting or illness.