Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare metabolic disorder that prevents the body from converting certain fats into energy, leading to severe complications during periods of fasting.
Overview
Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare condition that impairs the body's ability to break down certain fats for energy, particularly when a person goes without food. Signs and symptoms typically manifest during infancy or early childhood.
Symptoms and Clinical Features
The presentation of LCHAD deficiency can vary, with symptoms often triggered by physiological stress, such as fasting, viral infections, or extreme weather. This condition is sometimes mistaken for Reye syndrome, a severe disorder associated with aspirin use during recovery from viral infections like chickenpox or flu.
Infantile and Early Childhood Symptoms
- Feeding difficulties, including an extreme dislike of eating or certain foods (food or feeding aversion), nausea, and vomiting
- Lack of energy (lethargy)
- Low blood glucose (hypoglycemia)
- Weak muscle tone (hypotonia)
- Delayed developmental milestones
- Liver problems
- Abnormalities in the light-sensitive tissue at the back of the eye (the retina), which can cause impaired vision, nearsightedness (myopia), or night blindness that worsens over time
Later Childhood and Severe Complications
- Muscle pain and the breakdown of muscle tissue (rhabdomyolysis)
- Loss of sensation in the arms and legs (peripheral neuropathy)
- Weakened heart muscle (cardiomyopathy) and heart failure
- Breathing difficulties
- Coma and sudden death
Frequency
The exact incidence of LCHAD deficiency is unknown. One estimate from a Finnish population indicates an incidence of 1 in 62,000 pregnancies. The incidence in the United States is believed to be much lower.
Causes and Risk Factors
LCHAD deficiency is caused by variants (mutations) in the HADHA gene. This gene provides instructions for making a portion of an enzyme complex called the mitochondrial trifunctional protein, which operates within the cell's energy-producing centers (mitochondria).
This enzyme complex contains three enzymes that break down long-chain fatty acids, which are found in foods like milk and certain oils, and are stored in the body's fat tissues. These fatty acids serve as a major energy source for the heart, muscles, and liver (especially during fasting).
Variants in the HADHA gene disrupt one of the functions of this enzyme complex, preventing the normal processing of long-chain fatty acids. Because these fats cannot be converted into energy, individuals experience lethargy and hypoglycemia. Additionally, the abnormal buildup of unprocessed or partially metabolized fatty acids damages the liver, heart, muscles, and retina, causing the other primary symptoms of the disorder.
Inheritance
This condition is inherited in an autosomal recessive pattern. This means that both copies of the gene in each cell contain variants. The parents of an affected individual each carry one copy of the altered gene but typically do not exhibit any signs or symptoms of the condition.
Other Names for This Condition
- 3-hydroxyacyl-CoA dehydrogenase, long chain, deficiency
- LCHAD deficiency
- Long-chain 3-hydroxy acyl CoA dehydrogenase deficiency
- Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
- Long-chain 3-OH acyl-CoA dehydrogenase deficiency
- Trifunctional protein deficiency, type 1