Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below

Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.
2000 Apr 20 [updated 2012 Jan 19].

Excerpt

DISEASE CHARACTERISTICS:

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) is one of the enzymes involved in mitochondrial fatty acid β-oxidation, which fuels hepatic ketogenesis, a major source of energy once hepatic glycogen stores become depleted during prolonged fasting and periods of higher energy demands. In a typical clinical scenario, a previously healthy child with MCAD deficiency presents with hypoketotic hypoglycemia, vomiting, and lethargy triggered by a common illness. Seizures may occur. Hepatomegaly and liver disease are often present during an acute episode, which can quickly progress to coma and death. Children are normal at birth and – if not identified through newborn screening – typically present between ages three and 24 months; later presentation, even into adulthood, is possible. The prognosis is excellent once the diagnosis is established and frequent feedings are instituted to avoid any prolonged period of fasting.

DIAGNOSIS/TESTING:

Diagnosis requires the integrated interpretation of multiple analyses, including consideration of the clinical status of the affected individual (i.e., acutely symptomatic vs asymptomatic) at the time of sample collection. Initial testing should include the following analyses and their proper interpretation: Plasma acylcarnitines . Urine organic acids. Urine acylglycines . The biochemical diagnosis of MCAD deficiency can be confirmed by: Determination of fatty acid β-oxidation in fibroblasts; Measurement of MCAD enzyme activity in fibroblasts or other tissues; and/or . Molecular genetic testing of ACADM. The latter two tests can be used for prenatal diagnosis. Based on newborn screening results, approximately 50% of individuals are homozygous for the common mutation p.Lys304Glu, and approximately 40% are heterozygous for p.Lys304Glu and one of more than 90 rarer alleles.

MANAGEMENT:

Treatment of manifestations: Most important is giving simple carbohydrates by mouth (e.g., glucose tablets, or sweetened, non-diet beverages) or IV if needed to reverse catabolism and sustain anabolism. Prevention of primary manifestations: The mainstay is avoidance of fasting: infants require frequent feedings; toddlers could be placed on a relatively low-fat diet (e.g., <30% of total energy from fat) and could receive 2 g/kg of uncooked cornstarch at bedtime to ensure sufficient glucose overnight. Prevention of secondary complications: Weight control measures including proper nutrition and exercise. Agents/circumstances to avoid: Hypoglycemia (e.g., from excessive fasting); infant formulas that contain medium-chain triglycerides as the primary source of fat. Evaluation of relatives at risk: Evaluate plasma acylcarnitine concentration and urine acylglycine in sibs and parents to permit early diagnosis and treatment of previously asymptomatic at-risk family members.

GENETIC COUNSELING:

MCAD deficiency is inherited in an autosomal recessive manner. At conception, the sibs of an affected individual are at a 25% risk of being affected, a 50% risk of being asymptomatic carriers, and a 25% risk of being unaffected and not carriers. The risk of being affected could be 50% if one of the parents is also affected. Because asymptomatic parents and sibs may have MCAD deficiency, biochemical evaluation and/or molecular genetic testing should be offered to both parents and all sibs. Because of the high carrier frequency for the p.Lys304Glu mutation in individuals of northern European origin, carrier testing should be offered to reproductive partners of individuals with MCAD deficiency. Prenatal testing for pregnancies at 25% or higher risk is possible by biochemical methods or, if both parental mutations are known, by molecular genetic testing.

Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

PMID:
20301597
[PubMed]
Books & DocumentsFree full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Write to the Help Desk