Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency

  • Matern D
  • Rinaldo P
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Abstract

CLINICAL 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 of MCAD deficiency 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 plasma acylcarnitine analysis, urine organic acid analysis, and urine acylglycine analysis and their proper interpretation. Further confirmatory testing can be by identification of biallelic pathogenic variants in ACADM or additional biochemical genetic testing (i.e., determination of fatty acid β-oxidation flux in fibroblasts or measurement of MCAD enzyme activity in leukocytes, fibroblasts or other tissues). 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.,

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Authors

  • Dietrich Matern

  • Piero Rinaldo

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