LCHAD deficiency

Other Names: Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency; Long-chain 3-hydroxy acyl CoA dehydrogenase deficiency; Long-chain 3-OH acyl-CoA dehydrogenase deficiency; 3-hydroxyacyl-CoA dehydrogenase long chain deficiency

LCHAD deficiency, or long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, is a mitochondrial condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).

Epidemiology

The incidence of LCHAD deficiency is unknown. One estimate, based on a Finnish population, indicates that 1 in 62,000 pregnancies is affected by this disorder. In the United States, the incidence is probably much lower.

Cause

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. As the name suggests, mitochondrial trifunctional protein contains three enzymes that each perform a different function. This enzyme complex is required to break down (metabolize) a group of fats called long-chain fatty acids. Long-chain fatty acids are found in foods such as milk and certain oils. These fatty acids are stored in the body's fat tissues. 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. These mutations prevent the normal processing of long-chain fatty acids from food and body fat. As a result, these fatty acids are not converted to energy, which can lead to some features of this disorder, such as lethargy and hypoglycemia. Long-chain fatty acids or partially metabolized fatty acids may also build up and damage the liver, heart, muscles, and retina. This abnormal buildup causes the other signs and symptoms of LCHAD deficiency.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

Signs and symptoms of LCHAD deficiency typically appear during infancy or early childhood and can include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), weak muscle tone (hypotonia), liver problems, and abnormalities in the light-sensitive tissue at the back of the eye (retina). Later in childhood, people with this condition may experience muscle pain, breakdown of muscle tissue, and a loss of sensation in their arms and legs (peripheral neuropathy). Individuals with LCHAD deficiency are also at risk for serious heart problems, breathing difficulties, coma, and sudden death.

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. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Hypoketotic hypoglycemia
• Photophobia(Extreme sensitivity of the eyes to light)

30%-79% of people have these symptoms

• Abnormal electroretinogram
• Exotropia(Outward facing eye ball)
• Global developmental delay
• Hepatomegaly(Enlarged liver)
• Hypertrophic cardiomyopathy(Enlarged and thickened heart muscle)
• Peripheral neuropathy
• Visual loss(Loss of vision)

5%-29% of people have these symptoms

• Abnormality of retinal pigmentation
• Cholestatic liver disease
• Chorioretinal atrophy
• Failure to thrive(Faltering weight)
• Feeding difficulties(Feeding problems)
• Generalized hypotonia(Decreased muscle tone)
• Intellectual disability(Mental deficiency)
• Myopia(Close sighted)
• Nyctalopia(Night blindness)
• Posterior staphyloma
• Retinopathy(Noninflammatory retina disease)
• Seizure

Diagnosis

Biochemical Genetics Tests

• Enzyme assay
• Analyte

Molecular Genetics Tests

• Sequence analysis of the entire coding region
• Deletion/duplication analysis
• Sequence analysis of select exons
• Targeted variant analysis

Treatment

Treatment includes includes diet and low-dose carnitine supplements, as well as avoiding fasting.

NIH genetic and rare disease info

• NIH info on LCHAD deficiency

LCHAD deficiency is a rare disease.

LCHAD deficiency Resources
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