VLCAD Deficiency
From WikiGenetics
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[edit] Name of Condition
Very Long Chain Acyl-CoA Dehydrogenase Deficiency, known as VLCAD Deficiency.
[edit] Definition
VLCAD Deficiency is an inherited disorder where the body is unable to break down certain types of fats to use for energy. The symptoms are evident during infancy and require careful treatment. gemscool
In particular, patients are unable to break down fatty acids having 14 or more carbon atoms in the chain. Since many natural lipids, including those synthesized by humans like palmitic acid, have 16 or more carbons (stearic acid has 18), these can accumulate in the body and cause damage by obstructing Co-A in the mitochondria. Worse, since the body's fat stores including mostly these long chain fatty acids are only slowly metabolized for energy, patients may go hypoglycemic after prolonged exercise or after fasting -- even an overnight fast may be enough to cause problems.
[edit] Description, Signs and Symptoms
3 phenotypes are known. gemscool In one phenotype, symptoms of VCLAD Deficiency appear during infancy and include:
- hypoglycemia (low blood sugar) without ketones being present
- lethargy (lack of energy)
- muscle weakness
- cardiomyopathy
In another phenotype, symptoms arise in childhood, including
- hypoglycemia (low blood sugar) without ketones being present
- lethargy (lack of energy)
In another phenotype, symptoms may arise later in childhood or early adulthood and are triggered by exercise or fasting. These may include
- fatigue
- rhabdomyolysis
- myoglobinuria
The difference between phenotypes may depend on particular isoforms of impaired enzyme and amount of residual activity present. It may also depend on activity of alternative metabolic pathways, long chain acetyl co-a dehydrogenase may metabolize the very long chain fatty acids but at a greatly reduced rate.
[edit] Inheritance
VLCAD Deficiency is an inherited autosomal recessive disorder. It is caused by a mutation in the ACADVL gene, located on chromosome 17, which when functional produces an enzyme that breaks down fats. Without this enzyme, fats can build up in the body and cause damage to the liver, heart, and muscles.
[edit] Demographics
This disorder is estimated to affect between 1 in 40,000 and 1 in 120,000 people worldwide.
[edit] Diagnosis
[edit] Treatment and Management
Daily life:
Fasting and long term exercise must be avoided. In particular, fasting and exercise that normally requires catabolism of fat should be avoided. Fasting that should be avoided includes even short, overnight, fasts especially in the young -- children may need to be awakened for a bottle or fed a complex carbohydrate at bedtime so they can make it through the night. Frequent, small, high-carbohydrate and high-protein meals are required. Short-term exercise supportable by muscle and liver glycogen should not cause problems.
Diet must be modified, with intake of long chain fatty acids minimized, and medium chain fatty acids supplemented - usually as a medium chain triglyceride oil. This will likely mean a diet high in carbohydrates and isolated protein.
When crises occur:
Metabolic crises may be triggered by fasting, exercise, fever, or any illness that impairs eating and food absorption - for example anything that causes diarrhea, nausea or vomiting.
Protocols vary with phenotype. What is said here applies to many but not all patients.
IV glucose (10%) must be administered early and continuously to reduce catabolism of the patient's own fat stores -- because these fat stores have triglycerides containing high percentages of long-chain fatty acids.
Ideally, start IV glucose and draw blood samples as soon as possible after arrival at the ER. Glucose levels should maintained above 75 mg/dl.
Patients able to retain food should be fed often, especially if glucose levels are low. In some cases this may permit minimizing IV glucose.
If patients are unable to take food orally, parenteral nutrition (amino acids, glucose, and medium chain fatty acids) should be considered much earlier than with metabolically normal patients. This will help avoid entering the catabolic state.
Since crises can be triggered by other illnesses that interfere with regular food intake (e.g. ailments that cause nausea and vomiting, or surgery), look for and treat the triggering ailment.
[edit] Prognosis
[edit] Resources
AccessDNA.com - Very Long Chain Acyl-Coenzyme A Dehydrogenase Deficiency[1]
http://ghr.nlm.nih.gov/condition=verylongchainacylcoenzymeadehydrogenasedeficiency
[edit] References
http://ghr.nlm.nih.gov/condition=verylongchainacylcoenzymeadehydrogenasedeficiency
