Methylmalonic acidemia

Methylmalonic acidemia

Description, Causes and Risk Factors:

An inherited metabolic defect which results from a deficiency of propionyl Coenzyme A carboxylase, the enzyme that converts propionate to methylmalonate; the enzyme requires biotin as a cofactor; clinically, affected infants have overwhelming illness, with lethargy, metabolic acidosis with ketosis, hypotonia; coma and seizures typically develop with early death; propionic acid is markedly elevated in plasma and urine; there is also hyperammonemia, and elevated levels of other metabolites as well, including glycine, hence the original name for the syndrome.

Methylmalonic acidemia is a rare autosomal-recessive inborn error of metabolism which is caused by a downstream defect in the propionate metabolic pathway. Methylmalonyl-CoA mutase, the enzyme which converts methylmalonyl-CoA to succinyl-CoA is found to be nonfunctional in these disorders. The metabolic block in these disorders often leads to severe keto and organic acidosis, hyperammonemia, hyperglycinemia, and hypoglycemia with marked accumulation of methylmalonate in body fluids and tissues of infants and children. The clinical presentation and pathology is accordingly severe in these disorders: Widespread psychomotor dysfunction, failure to thrive, dystonia, and hepatomegaly are some of the symptoms and the symptoms can extend to long-term neurological and systemic impairment. Hematological abnormalities are also observed, especially in cases where methylmalonic acidemia is accompanied by homocystineuria. The disorder is lethal in its early (neonatal) onset form, and may also manifest as a chronic problem, with episodes of acute decompensation and, in rare cases, the patient may be completely asymptomatic (`benign' form).

The inherited forms of methylmalonic acidemia cause defects in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase. Vitamin B12 is also needed for the conversion of methylmalonyl-CoA to Succinyl-CoA. Mutations leading to defects in vitamin B12 metabolism or in its transport frequently result in the development of methylmalonic acidemia.

This disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene — one from each parent — must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

The disease is usually diagnosed in the first year of life. It is an autosomal recessive disorder, which means the defective gene must be passed onto the child from both parents.

About 1 in 25,000 - 48,000 babies are born with this condition. However, the actual rate may be higher, because a newborn may die before the condition is ever diagnosed. Methylmalonic acidemia affects boys and girls equally.



    Brain disease that gets worse (progressive encephalopathy).

  • Dehydration.

  • Developmental delays.

  • Failure to thrive.

  • Lethargy.

  • Repeated yeast infections.

  • Seizures.

  • Vomiting.


    Metabolic stroke (following episodes of metabolic decompensation).

  • Pancytopenia.

  • Neutropeniaand thrombocytopenia.

  • Anemia.

  • Susceptibility to viraland bacterialinfections.

  • Chronic renal insufficiency.

  • Hepatic steatosis.

  • Ataxia and mental retardation possibly resulting from demyelination of subcortical and other neurons andcharacteristic lesions in the globus pallidus (evident from MR and CT imaging).

  • Failure of linear growth (seen in some short and obese patients).

  • Acute pancreatitis (due to metabolic decompensation).


Testing for methylmalonic acidemia is often done as part of a newborn screening exam. The U.S. Department of Health and Human Services recommends screening for this condition at birth because early detection and treatment has been shown to be beneficial.

Tests that may be done to diagnose this condition include:

    Ammonia test.

  • Blood gases.

  • Complete blood count (CBC).

  • CT scan or MRI of the brain.

  • Electrolyte levels.

  • Genetic testing.

  • Methylmalonic acid blood test.

  • Plasma amino acid test.


Treatment consists of cobalamin and carnitine supplements and a low-protein diet. The child's diet must be carefully controlled. If supplements do not help, the doctor may also recommend a diet that avoids substances called isoleucine, threonine, methionine, and valine.

Liver or kidney transplantation (or both) have been shown to help some patients. These transplants provide the body with new cells that help breakdown methylmalonic acid normally.

NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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