Very long-chain acyl-coenzyme A dehydrogenase deficiency

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Very long-chain acyl-coenzyme A dehydrogenase deficiency
Synonyms VLCADD, VLCAD deficiency
Pronounce
Field Genetics, Metabolic disorders, Pediatrics
Symptoms Hypoglycemia, lethargy, hepatomegaly, cardiomyopathy, muscle pain, hypotonia
Complications Metabolic crisis, seizure, coma, cardiac arrest
Onset Neonatal to adulthood
Duration Chronic
Types Early-onset, childhood-onset, and adult-onset forms
Causes Mutation in the ACADVL gene
Risks Consanguinity, family history
Diagnosis Newborn screening, plasma acylcarnitine profile, enzyme assay, genetic testing
Differential diagnosis Medium-chain acyl-CoA dehydrogenase deficiency, Reye syndrome, sepsis, glycogen storage disease
Prevention Avoidance of fasting, regular feeding schedules
Treatment Dietary management, glucose supplementation during illness, emergency protocol
Medication Medium-chain triglyceride (MCT) oil, L-carnitine (in select cases)
Prognosis Variable; improved with early detection and treatment
Frequency ~1 in 30,000 to 100,000 births (varies by population)
Deaths Can be fatal without treatment; mortality reduced with early diagnosis


Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD or VLCAD deficiency) is a rare inborn error of metabolism that affects the body’s ability to break down very long-chain fatty acids into usable forms of energy, especially during times of fasting or increased energy demands.

It is caused by mutations in the ACADVL gene, which provides instructions for making an enzyme necessary for the first step in the mitochondrial beta-oxidation of long-chain fatty acids. This enzyme deficiency leads to the accumulation of unmetabolized fatty acids and a lack of cellular energy, particularly affecting the liver, heart, and skeletal muscles.

Signs and symptoms[edit | edit source]

The clinical presentation of VLCADD varies widely depending on the age of onset. There are three major forms:

Genetics[edit | edit source]

VLCADD is inherited in an autosomal recessive pattern. Mutations in the ACADVL gene (located on chromosome 17p13.1) result in defective or deficient activity of the VLCAD enzyme. Over 80 different mutations in the ACADVL gene have been identified. Homozygous or compound heterozygous mutations are required for disease manifestation.

Heterozygous carriers are typically asymptomatic but may show mild biochemical abnormalities.

Pathophysiology[edit | edit source]

The VLCAD enzyme is responsible for the initial step in the breakdown of very long-chain fatty acids (C14–C20) in the mitochondria. Its absence leads to energy deficits, particularly during fasting or catabolic stress, as the body becomes unable to generate energy from fat stores. Accumulation of toxic intermediates can damage organs, particularly the heart and muscles.

Diagnosis[edit | edit source]

Diagnosis is often made via newborn screening, which detects abnormal levels of acylcarnitines (especially elevated C14:1) in blood spots. Confirmatory tests include:

Treatment[edit | edit source]

There is no cure for VLCADD, but symptoms can be managed with:

  • Avoidance of fasting: frequent meals and overnight feeds in infants
  • Dietary modifications:
    • Low-fat, high-carbohydrate diet
    • Use of medium-chain triglyceride (MCT) oil, which bypasses the VLCAD-dependent metabolic pathway
  • Emergency care:
    • Prompt treatment of illness or fasting with IV glucose
  • Carnitine supplementation: controversial; may be used in select cases under medical supervision
  • Monitoring for cardiomyopathy and rhabdomyolysis

Prognosis[edit | edit source]

With early detection and proper management, many children with VLCADD can lead relatively normal lives. However, the early-onset form is associated with increased risk of mortality, particularly if undiagnosed. Long-term outcomes depend on the severity of the enzyme deficiency and the timing of treatment.

Epidemiology[edit | edit source]

VLCADD occurs in approximately 1 in 30,000 to 100,000 live births, though the frequency varies among populations. Newborn screening programs have increased the detection rate and improved outcomes through early intervention.

See also[edit | edit source]

References[edit | edit source]


External links[edit | edit source]



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External resources



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