ACADM gene
Also known as: ACADM deficiency; MCAD deficiency; MCADH deficiency; Carnitine deficiency secondary to medium-chain acyl-coa dehydrogenase deficiency
OMIM#201450 https://omim.org/entry/201450
1. The Disease
Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD) is an inherited disorder of fatty acid β oxidation metabolism caused by mutations in the ACADM gene. MCAD is inherited in an autosomal recessive pattern – a mutation must be present in the copies inherited from both the mother and the father – for the disease to manifest itself. The enzyme deficiency is medium-chain acyl-CoA dehydrogenase, one of the four-mitochondrial acyl-CoA dehydrogenases that carry out the first steps of β oxidation. MCAD deficiency results in an impaired ability to oxidize fatty acids of medium-chain length (C6-C12).
2. The Symptoms
Infants are usually asymptomatic at birth and in the neonatal period. Symptoms often appear between the second months to the second year of life, but onset as early as 2 days and as late as adulthood has been reported. Lack of early signs or symptoms does not exclude the diagnosis.
- Infants present with vomiting, lethargy, apnea, coma, cardiopulmonary arrest, or sudden unexplained death (SIDS), triggered by a seemingly innocuous illness such as otitis or viral infection. Profound hypoglycemia can occur after prolonged fasting.
- Left untreated, MCAD results in severe hypoglycemia. During acute illness, the child can present with mild to moderate hepatomegaly, and sometimes, muscle weakness. Early detection and treatment is important to normal life.
- MCAD accounts for 1% of all SIDS cases, even in the absence of signs of metabolic illness.
3. Actions to take in case of early diagnosis
- Infants with a positive genetic test (having 2 mutations or 2 copies of a single mutations in the ACADM gene) should continue breastfeeding.
- Early treatment, through fatty acid restriction and the avoidance of prolonged periods of fasting, is essential in preventing metabolic crises and chronic symptoms, such as hepatic and muscle impairment.
- Infants with a positive genetic test should have confirmatory MCAD testing through one of the following methods:
- Tandem mass spectrometry (MS/MS) for the detection of elevated levels of octanoylcarnitine (C8), decanoyl (C10), hexanoyl (C6) and decenoyl (C10:1) carnitine esters and their ratios C8/C0 or C8/C10.
- Urinary acylglycines – increase in suberylglycine and hexanoylglycine.
- MCAD is a lifelong disease that requires lifetime compliance to dietary management and regular follow-up with a metabolic disease specialist and a multidisciplinary approach.
- The prognosis for MCAD is very favorable with lifetime compliance to a low-fat diet and fractionated meals.
- Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
4. For more information
Biblio: https://www.ncbi.nlm.nih.gov/books/NBK1424/