Very long-chain acyl-coenzyme A dehydrogenase deficiency
Very long-chain acyl-coenzyme A dehydrogenase deficiency is a fatty-acid metabolism disorder which prevents the body from converting certain fats to energy, particularly during periods without food.
Those affected by this disorder have inadequate levels of an enzyme that breaks down a group of fats called very long-chain fatty acids.
Signs and symptoms
Signs and symptoms can include:- hypoglycemia
- lethargy
- hepatomegaly
- muscle pain
- cardiomyopathy
- Early onset-pericardial effusion
- heart arrhythmias
- vomiting
- Coma
- Death
- Rhabdomyolysis
- Hypoketotic Hypoglycemia
Causes
VLCAD deficiency is exclusively linked to genetic mutations in DNA. A change of the gene that codes for very long-chain-acyl-CoA-dehydrogenase results in a deficiency or malfunction of the produced VLCAD enzyme. This mutation occurs on chromosome 17 and can be altered via a variety of pathways. These can range from frameshift mutations, deletion mutations, insertion mutations, and missense mutations. All of which cause the enzyme to function differently in the mitochondria, or in some cases not at all. Due to this mutation, effective levels of very long-chain-acyl-CoA-dehydrogenase are low or absent in the body, giving rise to the array of symptoms listed above.Genetics
Mutations in the ACADVL gene lead to inadequate levels of an enzyme called very long-chain acyl-coenzyme A dehydrogenase. Without this enzyme, long-chain fatty acids from food and fats stored in the body cannot be degraded and processed. As a result, these fatty acids are not converted into energy, which can lead to characteristic signs and symptoms of this disorder, such as lethargy and hypoglycemia. Levels of very long-chain fatty acids or partially degraded fatty acids may build up in tissues and can damage the heart, liver, and muscles, causing more serious complications.VLCAD deficiency is characterized as an inherited genetic disorder. The mutations that occur within the gene itself are recessive, meaning that an individual has to acquire both recessive mutated genes in order for the disease to manifest. There are various forms of the disease that can be manifested in infancy, adolescence, and adulthood. However, it is still unknown at to what causes the disease to manifest itself in the different life stages.
Diagnosis
Typically, initial signs and symptoms of this disorder occur during infancy and include low blood sugar, lack of energy, and muscle weakness. There is also a high risk of complications such as liver abnormalities and life-threatening heart problems. Symptoms that begin later in childhood, adolescence, or adulthood tend to be milder and usually do not involve heart problems. Episodes of very long-chain acyl-coenzyme A dehydrogenase deficiency can be triggered by periods of fasting, illness, and exercise.It is common for babies and children with the early and childhood types of VLCAD to have episodes of illness known as metabolic crises. Some of the first symptoms of a metabolic crisis are: extreme sleepiness, behavior changes, irritable mood, poor appetite.
Some of these other symptoms of VLCAD in infants may also follow: fever, nausea, diarrhea, vomiting, hypoglycemia. Evaluation of symptom combinations can aid in a positive diagnosis of VLCAD. Since symptoms vary depending on age and onset of the patient, consultation with a metabolic specialist should be considered. Diagnosis is further confirmed through genetic analysis of the VLCAD gene.