Also known as: VLCAD deficiency OMIM#201475

1. The Disease

Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is an inherited disorder of mitochondrial long-1. chain fatty acid oxidation with a variable presentation including: cardiomyopathy, hypoketotic hypoglycemia, liver disease, exercise intolerance and rhabdomyolysis.

2. The Symptoms

Infants are usually asymptomatic at birth. Lack of early signs or symptoms does not exclude the diagnosis. VLCADD is a clinically heterogeneous disease, with 3 major phenotypes:

  • Severe infantile VLCADD has an early onset, usually within the first 3-12 months of life and as early as the neonatal period, with high mortality and a high incidence of hypoketotic hypoglycaemia, liver disease, cardiac arrhythmias and cardiomyopathy. Pericardial effusion is also reported.
  • Moderately severe infantile/childhood VLCADD has a later onset (early neonatal period to early childhood) and usually presents with hypoketotic hypoglycemia, lower mortality and rarely cardiomyopathy.
  • Late-onset myopathic VLCADD presents in older children and young adults (usually >10 years of age) with isolated skeletal muscle involvement, exercise intolerance, myalgia, rhabdomyolysis and myoglobinuria usually triggered by exercise, fasting, cold/heat and/or stress but viral infection can also precipitate/exacerbate this presentation. In rare cases it can lead to renal failure and can be fatal. Some patients presenting with myopathic disease may have a previous history of hypoglycemia in infancy/childhood.

3. Actions to take in case of early diagnosis

  • Babies with a positive genetic test (having 2 mutations or 2 copies of a single mutations in the ACADVL gene) should continue breastfeeding.
  • Babies with a positive genetic test should have confirmatory VLCAD testing through one of the following methods:
  • Tandem mass spectrometry (MS/MS) for the detection of elevated levels of C14:1 and C14:1/C12:1 ratios together with elevations of C12, C16, C16:1, C18 and C18:1 species. Occasionally patients with the myopathic form can give an essentially normal profile when metabolically stable.
  • Crisis urine organic acid analysis generally shows a non-specific abnormal pattern of C6-C14 dicarboxylic and hydroxydicarboxylic acids.
  • VLCAD is a lifelong disease that requires lifetime compliance to dietary management and regular follow-up with a metabolic disease specialist and a multidisciplinary approach.
  • 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.
  • Diet consists of low long-chain fat source in combination with medium chain triglycerides.
  • The prognosis for VLCAD 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