What is methylmalonic acidemia?

Methylmalonic acidemia (MMA) is a rare, genetic disorder of the liver. People with this condition are unable to produce an enzyme that is needed to break down and use certain proteins and fats found in food. This causes a buildup of acids and other harmful substances in the blood, urine and other cells, including brain cells. The disease is most often diagnosed within the first few months of life.

How this toxic buildup affects the body can vary drastically from one person to another. For some, it causes seizures, strokes, growth problems, developmental delays and frequent episodes of severe illness.

Causes

MMA is a genetic disorder, meaning it is passed down through families. The faulty gene (a mutation) must be passed down to a child from both parents.

Symptoms

Methylmalonic acidemia causes episodes of severe illness called decompensation events, which are the result of the build-up of toxic substances in the blood. The first decompensation event usually occurs a few days after birth. Symptoms may include:

• Poor feeding and loss of appetite
• Vomiting
• Weak muscle tone (hypotonia)
• Lack of energy (lethargy)
• Seizures
• Coma

Over time, MMA can result in serious complications, such as enlarged liver, kidney failure, intellectual and motor disability, and vision problems.

How is methylmalonic acidemia diagnosed?

Methylmalonic acidemia can be diagnosed through newborn screening. Additional genetic testing can verify the diagnosis.

Treatment

Treatment focuses on managing the symptoms. People with MMA must follow a special low-protein diet. Certain medications and antibiotics can be a part of the treatment plan, and people with a particular variation of the disease benefit from vitamin B12 supplements.

For children with MMA, Children’s Hospital of Philadelphia offers a multidisciplinary team that works together to care for patients. Team members might include a dietitian, geneticist, neurologist, ophthalmologist, nephrologist, and physical and occupational therapists.

In some cases, liver transplantation can help children with methylmalonic acidemia lead a more normal life. The healthy transplanted liver expresses the normal enzymes necessary to process dietary proteins. In some cases, patients with MMA may also require kidney transplant.