What is Lchad disease?
What is Lchad disease?
Overview. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).
What is acyl dehydrogenase deficiency?
Overview. Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inherited disorder that prevents your body from breaking down certain fats and converting them into energy. As a result, the level of sugar in your blood can drop dangerously low (hypoglycemia).
What does acyl-CoA Dehydrogenase do?
The acyl-CoA dehydrogenases (ACADs) are enzymes that catalyze the α,β-dehydrogenation of acyl-CoA esters in fatty acid and amino acid catabolism. Eleven ACADs are now recognized in the sequenced human genome, and several homologs have been reported from bacteria, fungi, plants, and nematodes.
Why does MCAD deficiency cause hyperammonemia?
FAO is defective in MCAD deficiency and may rapidly lead to hypoglycemia and hypoketosis when body needs FAO to produce energy. The accumulating medium-chain fatty acids such as C8 (octanoate) and other medium-chain acyl-CoAs may have toxic effects, which disrupt urea cycle and may cause hyperammonemia.
How is Lchad diagnosed?
The diagnosis is confirmed by mutation analysis of the two genes (HADHA and HADHB) encoding for the alpha and beta subunits of the enzyme. The most common mutation causing LCHAD deficiency is c.
Is Lchad genetic?
LCHAD is an autosomal recessive genetic conditionAn illness caused by abnormalities in genes or chromosomes.
How do you manage MCAD deficiency?
Strategies may include:
- Taking simple carbohydrates, such as sugar (glucose) tablets or sweetened, nondiet beverages.
- Seeking emergency medical care if unable to eat or for diarrhea or vomiting. An intravenous (IV) line for extra glucose and additional treatment may be needed.
How common is MCAD deficiency?
In the United States, the estimated incidence of MCAD deficiency is 1 in 17,000 people. The condition is more common in people of northern European ancestry than in other ethnic groups.
Where is acyl-CoA dehydrogenase found?
mitochondria
Acyl-CoA dehydrogenases (ACADs), flavoproteins found in the mitochondria, are involved in β-oxidation of fatty acids.
How is Mcadd diagnosed?
MCADD is usually diagnosed through newborn screening by a blood test. The test looks for the amount of chemicals known as acylcarnitines. High levels of a type of acylcarnitine called octanoylcarnitine are characteristic of MCADD, but this is not specific to this disorder.
Why does fatty acid oxidation occur?
Fatty acid oxidation also occurs in peroxisomes when the fatty acid chains are too long to be handled by the mitochondria. The same enzymes are used in peroxisomes as in the mitochondrial matrix, and acetyl-CoA is generated.
What is hyperammonemia?
Hyperammonemia is a metabolic condition characterized by elevated levels of ammonia in the blood.
When does long chain CoA dehydrogenase deficiency occur?
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).
How does mutation in HADHA gene cause LCHAD deficiency?
Mutations in the HADHA gene cause LCHAD deficiency. The HADHA gene provides instructions for making part of an enzyme complex called mitochondrial trifunctional protein. This enzyme complex functions in mitochondria, the energy-producing centers within cells.
When do problems related to LCHAD deficiency occur?
Problems related to LCHAD deficiency can be triggered when the body is under stress, for example during periods of fasting, illnesses such as viral infections, or weather extremes.
How does the HADHA gene affect the liver?
Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues. Mutations in the HADHA gene that cause LCHAD deficiency disrupt one of the functions of this enzyme complex.