Multiple acyl-CoA dehydrogenase deficiency (MADD)
MADD is inherited in an autosomal recessive pattern. Normally a person has two functional genes. In people with MADD, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with MADD 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 MADD do not typically have symptoms.
There is a wide range of symptoms in MADD. Patients with neonatal onset may develop hypoglycemia (low blood sugar), hyperammonaemia (elevated ammonia), hypotonia (low muscle tone) and hepatomegaly (enlarged liver). Some patients also have congenital birth defects. Symptoms of the later onset, less severe type of MADD may include any combination of hypoglycemia (low blood sugar), liver dysfunction, cardiomyopathy (heart muscle disease), recurrent infections and muscle weakness.
- Incidence: MADD is very rare. The incidence is unknown.
- New York State Method of Screening (First Tier): Screening for MADD is accomplished by measuring acylcarnitines (C6 and C8) by tandem mass spectrometry (MS/MS). Other acylcarnitines including C4, C5, C14, C16 and C16OH may also be elevated.
- Second Tier Screening: None
- Testing can be affected by: C8 may be elevated in infants fed MCT oil or taking valproate.
- Interpretation/reporting of data: Results are reported as screen negative, 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 MADD are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of MADD.
Diagnostic testing may include quantification of plasma acylcarnitines, urine acylglycines, urine organic acid analysis, molecular genetic testing of the ETFA, ETFB, and ETFDH genes and functional analysis of fatty acid oxidation on fibroblasts (skin cells).
Patients with mild MADD may benefit from treatment with riboflavin. Dietary modifications may also be recommended.
Prognosis is good for patients with mild MADD who respond to riboflavin. Patients with neonatal onset MADD typically die in the first days to weeks of life.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a disorder of fatty acid oxidation (inherited metabolic disorder).
MADD is caused by mutations in one of three genes, ETFA, ETFB, or ETFDH. Individuals with this disorder are unable to convert certain fats to energy and may have symptoms during times of high energy need such as fasting or illness.