MCAD deficiency is inherited in an autosomal recessive pattern. Normally a person has two ACADM genes. In people with MCAD deficiency, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with MCAD 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 MCAD deficiency do not typically have symptoms.
Newborns may not show any symptoms, but left untreated, the disorder can cause hypoglycemia, lethargy, liver disease, vomiting, seizures, coma and sudden death.
- Incidence: The incidence is approximately 1 in 17,000 in the United States. MCAD deficiency is more common in those with Northern European ancestry.
- New York Method of Screening (First Tier): Screening for MCAD deficiency is accomplished by measuring acylcarnitines (C6 and C8) by tandem mass spectrometry (MS/MS).
- Second Tier Screening: If an elevation of C8 is identified, DNA testing is performed for a single common mutation, p.K329E. In the literature, approximately 90% of people with MCAD deficiency have at least one p.K329E mutation. However, a p.K329E mutation has been identified in 45 to 55% of patients with MCAD deficiency in NYS.
- Testing can be affected by: C8 may be elevated in infants fed medium-chain triglycerides (MCT) oil or taking valproate.
- Interpretation/reporting of data: Results are reported as within acceptable limits, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for MCAD deficiency are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of MCAD deficiency.
Diagnostic testing includes quantification of plasma acylcarnitines, urine organic acids, and urine acylglycines. Molecular genetic testing of the ACADM gene may be used for confirmation of the diagnosis.
There is no cure for the disorder. In infancy, treatment includes frequent feeding. Treatment includes lifelong avoidance of fasting. Some physicians may recommend consuming uncooked cornstarch before bedtime. Additional medical care, including intravenous feedings, may be required during times of illness.
The best results occur in those individuals identified by newborn screening and treated shortly after birth. The prognosis is excellent in patients who avoid fasting and seek additional treatment during times of illness.
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a fatty acid oxidation disorder (inherited metabolic disorder).
MCAD deficiency is caused by mutations in the ACADM gene. Individuals with this disorder are unable to convert certain fats to energy and may have symptoms during times of high energy need such as when fasting or ill.