Methylmalonic acidemia

Definition

Methylmalonic acidemia is an inherited disorder that is usually diagnosed in infancy. It causes the accumulation of methylmalonic acid in the body and can lead to severe metabolic problems.

Causes, incidence, and risk factors

People with this disease can't change, or "metabolize," an enzyme called methymalonyl-coenzyme A. The result is a buildup of methylmalonic acid in the body.

The disease is usually diagnosed in the first year of life. It is an autosomal recessive disorder, which means the defective gene must be inherited from both parents. About 1 in 25,000 - 48,000 babies are born with this condition. The true rate of occurrence of the disease may be higher, because many newborn may die from an undiagnosed case. Both boys and girls are equally affected.

Symptoms

The disease can cause seizures and stroke. Babies may appear normal at birth, but develop symptoms once start eating more protein, which can cause the condition to get worse. Symptoms include:

• Vomiting
• Dehydration
• Lethargy
• Seizures
• Failure to thrive
• Recurrent infections with Candida
• Progressive encephalopathy
• Developmental delays

Signs and tests

A number of different laboratory and radiology tests may be performed, including:

• Serum electrolytes
• Blood gas for acidosis
• Serum ammonia levels (see ammonia - test )
• Serum and urine tests for amino acids and organic acids
• Serum methylmalonic acid levels
• Enzyme analysis of fibroblasts for the specific enzyme defect
• CBC for neutropenia, anemia, and thrombocytopenia
• CT scan or MRI of the brain following a seizure

Treatment

Treatment consists of dietary supplementation with cobalamin, carnitine, and protein restriction.

If cobalamine supplementation doesn't help, a diet restricting isoleucine, threonine, methionine, and valine may be useful.

Expectations (prognosis)

Unfortunately, affected patients may not survive their first attack.

Complications

• Coma
• Death

Calling your health care provider

Parents or care-givers of a child with a first seizure should immediately seek medical attention. Infants with failure-to-thrive or developmental delays should see a pediatrician. Adults and children with strokes or acute mental status changes should seek immediate medical attention.

Prevention

A low-protein maintenance diet can help to reduce recurrent attacks of acidemia. Patients should also avoid people who are sick. Parents of a child with this disorder or couples desiring children who have a known family history of this disorder should seek information on genetic counseling.