Methylmalonic acidemia represents a group of disorders that affect the way a person breaks down proteins and fats. In general, symptoms of methylmalonic acidemia can occur from any time between the neonatal period and adulthood. There are two enzymatic subtypes of MUT-related methylmalonic acidemia:
The mut0 enzymatic subtype is usually associated with onset of symptoms shortly after birth. During metabolic decompensation (episodic crisis due to infection or other external stressors), symptoms include vomiting, dehydration, lethargy, seizures, too much acid in the blood (metabolic acidosis), and elevated ammonia levels in the blood (hyperammonemia). Long-term complications can include increased risk for infections, low muscle tone (hypotonia), brain damage (encephalopathy), epilepsy, developmental delay and intellectual disability, anorexia and poor growth (failure to thrive), pancreatitis, enlarged liver (hepatomegaly), and chronic kidney disease that progresses to kidney failure.
The mut- enzymatic subtype is usually associated with onset of symptoms by early infancy/childhood. Symptoms may be similar to the mut0 type, but there may be fewer complications. Symptoms often first present during metabolic decompensation and may include vomiting, dehydration, and lethargy. Long-term complications can include low muscle tone (hypotonia), developmental delay and intellectual disability, anorexia and poor growth (failure to thrive), chronic kidney disease, and pancreatitis.
The worldwide incidence of methylmalonic acidemia has not been studied. However, overall estimates for those populations studied are between 1 in 6,000 and 1/300,000. These incidences vary significantly likely due to regional differences, which may be in part due to founder effects (high frequency of disease because the group arose from a small, possibly isolated population). The portion of methylmalonic acidemia attributed to mutations in MUT is estimated to be ~63% based on one study in Europe.
There is no cure for methylmalonic acidemia. Treatment is divided between managing an acute crisis (metabolic decompensation) and management of symptoms between crises. Metabolic crisis is managed in a hospital and involves increasing the amount of fluid in the body, ensuring proper nutrition (reduced or no protein and increased glucose-intake), and monitoring laboratory work for signs of further complications (like those related to elevated ammonia levels), which is best done by a metabolic expert. Long-term management includes a high-calorie diet that is low in protein, hydroxocobalamin (vitamin B12) intramuscular injections for the mut- type, carnitine and other supplements, and antibiotics. Transplant may become necessary if organ failure occurs.
Methylmalonic acidemia is associated with a number of chronic issues and higher than average mortality rates. Even with treatment, the mut type can be associated with symptoms, like intellectual disability or kidney failure. Metabolic crisis can lead to coma, especially if left untreated, and the average age of death for patients with the mut type is ~3 years.
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Explanations of an extensive number of genetic diseases written for the public by the U.S. government's National Institutes of Health.