3-alpha hydroxyacyl-CoA dehydrogenase deficiency

Alternate names

3-hydroxylacyl-CoA dehydrogenase deficiency; Medium and short chain 3-hydroxyacyl-CoA dehydrogenase deficiency; M/SCHAD; HADH deficiency

Definition

3-hydroxyacyl-CoA dehydrogenase deficiency is an inherited condition that prevents the body from converting certain fats to energy, particularly during prolonged periods without food (fasting).

Epidemiology

The exact incidence of 3-hydroxyacyl-CoA dehydrogenase deficiency is unknown; it has been reported in only a small number of people worldwide.

Cause

• Mutations in the HADH gene cause 3-hydroxyacyl-CoA dehydrogenase deficiency.
• The HADH gene provides instructions for making an enzyme called 3-hydroxyacyl-CoA dehydrogenase.
• Normally, through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to break down (metabolize) fats and convert them to energy.
• The 3-hydroxyacyl-CoA dehydrogenase enzyme is required for a step that metabolizes groups of fats called medium-chain fatty acids and short-chain fatty acids.

Gene mutations

• Mutations in the HADH gene lead to a shortage of 3-hydroxyacyl-CoA dehydrogenase.
• Medium-chain and short-chain fatty acids cannot be metabolized properly without sufficient levels of this enzyme.
• As a result, these fatty acids are not converted to energy, which can lead to characteristic features of 3-hydroxyacyl-CoA dehydrogenase deficiency, such as lethargy and hypoglycemia.
• Medium-chain and short-chain fatty acids that are not broken down can build up in tissues and damage the liver, heart, and muscles, causing serious complications.
• Conditions that disrupt the metabolism of fatty acids, including 3-hydroxyacyl-CoA dehydrogenase deficiency, are known as fatty acid oxidation disorders.

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

• Initial signs and symptoms of this disorder typically occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, and lack of energy (lethargy).
• Affected individuals can also have muscle weakness (hypotonia), liver problems, low blood sugar (hypoglycemia), and abnormally high levels of insulin (hyperinsulinism).
• Insulin controls the amount of sugar that moves from the blood into cells for conversion to energy.
• Individuals with 3-hydroxyacyl-CoA dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden death.
• This condition may explain some cases of sudden infant death syndrome (SIDS), which is defined as unexplained death in babies younger than 1 year.
• Problems related to 3-hydroxyacyl-CoA dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections.
• 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.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 100% of people have these symptoms

• Decreased 3-hydroxyacyl-CoA dehydrogenase level

80%-99% of people have these symptoms

• Abnormal circulating acetylcarnitine concentration
• Confusion(Disorientation)
• Diarrhea(Watery stool)
• Dicarboxylic aciduria
• Elevated hepatic transaminase(High liver enzymes)
• Fasting hyperinsulinemia
• High blood insulin levels while fasting
• Hepatic steatosis(Fatty infiltration of liver)
• Hyperinsulinemic hypoglycemia
• Hypoglycemic encephalopathy
• Hypoglycemic seizures
• Hypoketotic hypoglycemia
• Increased circulating free fatty acid level
• Increased C-peptide level
• Intrauterine growth retardation(Prenatal growth deficiency)
• Lethargy
• Neonatal hypoglycemia(Low blood sugar in newborn)
• Neonatal hypotonia(Low muscle tone, in neonatal onset)
• Proportionate short stature
• Vomiting(Throwing up)

5%-29% of people have these symptoms

• Decreased plasma carnitine
• Failure to thrive(Faltering weight)
• Feeding difficulties in infancy
• Hyperammonemia(High blood ammonia levels)
• Lactic acidosis(Increased lactate in body)
• Mildly elevated creatine kinase
• Motor delay
• Peripheral neuropathy
• Pigmentary retinopathy
• Prolonged prothrombin time

1%-4% of people have these symptoms

• Acute hepatic failure(Acute liver failure)
• Dilated cardiomyopathy(Stretched and thinned heart muscle)
• Hepatic necrosis
• Hypertrophic cardiomyopathy(Enlarged and thickened heart muscle)
• Myoglobinuria
• Prolonged QT interval

Diagnosis

• Genetic testing is available for M/SCHAD.
• M/SCHAD can be confirmed by special test fatty acid oxidation probe using a skin sample.

Treatment

The following treatments are recommended for this condition:

• Avoid going long time without food
• Diet:Somtimes low fat, high carbohydrate diet is recommended for this condition
• L-carnitine supplements

NIH genetic and rare disease info

• NIH info on 3-alpha hydroxyacyl-CoA dehydrogenase deficiency

3-alpha hydroxyacyl-CoA dehydrogenase deficiency is a rare disease.

3-alpha hydroxyacyl-CoA dehydrogenase deficiency Resources
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