Very long-chain acyl-coenzyme A dehydrogenase deficiency
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:
- Neonatal/early-onset form:
- Hypoketotic hypoglycemia
- Cardiomyopathy (especially hypertrophic type)
- Hepatomegaly and liver dysfunction
- Arrhythmias and risk of sudden cardiac death
- Hypotonia and poor feeding
- Childhood-onset form:
- Episodes of metabolic crisis
- Vomiting, lethargy, muscle weakness
- Rhabdomyolysis and liver dysfunction
- Mild to moderate developmental delay
- Late-onset/adult form:
- Recurrent muscle pain, exercise intolerance, myopathy
- Rhabdomyolysis triggered by prolonged exercise or fasting
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:
- Plasma acylcarnitine profile via tandem mass spectrometry
- Urine organic acid analysis
- Enzyme assay in cultured fibroblasts
- Molecular genetic testing of the ACADVL gene
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]
- Fatty-acid metabolism disorder
- Medium-chain acyl-CoA dehydrogenase deficiency
- Inborn errors of metabolism
- Metabolic crisis
- Newborn screening
References[edit | edit source]
External links[edit | edit source]
Search WikiMD
Ad.Tired of being Overweight? Try W8MD's physician weight loss program.
Semaglutide (Ozempic / Wegovy and Tirzepatide (Mounjaro / Zepbound) available.
Advertise on WikiMD
WikiMD's Wellness Encyclopedia |
Let Food Be Thy Medicine Medicine Thy Food - Hippocrates |
Translate this page: - East Asian
中文,
日本,
한국어,
South Asian
हिन्दी,
தமிழ்,
తెలుగు,
Urdu,
ಕನ್ನಡ,
Southeast Asian
Indonesian,
Vietnamese,
Thai,
မြန်မာဘာသာ,
বাংলা
European
español,
Deutsch,
français,
Greek,
português do Brasil,
polski,
română,
русский,
Nederlands,
norsk,
svenska,
suomi,
Italian
Middle Eastern & African
عربى,
Turkish,
Persian,
Hebrew,
Afrikaans,
isiZulu,
Kiswahili,
Other
Bulgarian,
Hungarian,
Czech,
Swedish,
മലയാളം,
मराठी,
ਪੰਜਾਬੀ,
ગુજરાતી,
Portuguese,
Ukrainian
Medical Disclaimer: WikiMD is not a substitute for professional medical advice. The information on WikiMD is provided as an information resource only, may be incorrect, outdated or misleading, and is not to be used or relied on for any diagnostic or treatment purposes. Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition. WikiMD expressly disclaims responsibility, and shall have no liability, for any damages, loss, injury, or liability whatsoever suffered as a result of your reliance on the information contained in this site. By visiting this site you agree to the foregoing terms and conditions, which may from time to time be changed or supplemented by WikiMD. If you do not agree to the foregoing terms and conditions, you should not enter or use this site. See full disclaimer.
Credits:Most images are courtesy of Wikimedia commons, and templates, categories Wikipedia, licensed under CC BY SA or similar.
Contributors: Prab R. Tumpati, MD