Methylmalonic Acidaemia

What is methylmalonic acidaemia?

Methylmalonic acidaemia is an inherited disorder in which the body is unable to process certain proteins and fats (lipids) properly. The effects of methylmalonic acidaemia vary from mild to life-threatening. This condition, which usually appears in early infancy, is characterised by vomiting, dehydration, weak muscle tone (hypotonia), and excessive tiredness (lethargy). Without treatment, the disorder can lead to coma and death in some cases.

How common is methylmalonic acidaemia?

This condition occurs in 1 in 25,000 to 48,000 people.

What genes are related to methylmalonic acidaemia?

Mutations in the MMAA, MMAB, and MUT genes cause methylmalonic acidaemia.

About half of methylmalonic acidaemia cases are caused by mutations in the MUT gene. This gene provides instructions for making an enzyme called methylmalonyl CoA mutase, which is responsible for one step in the breakdown of several amino acids (the building blocks of proteins), certain lipids, and cholesterol. Mutations in the MUT gene alter the structure or reduce the amount of the enzyme, which prevents these molecules from being broken down properly. As a result, a substance called methylmalonyl CoA and other potentially toxic compounds can accumulate, causing the signs and symptoms of methylmalonic acidaemia.

Mutations in the MUT gene that prevent the production of any functional enzyme result in a form of the condition designated mut0. Mutations that change the structure of methylmalonyl CoA mutase but do not eliminate its activity cause a form of the condition designated mut-.

Other cases of methylmalonic acidaemia are caused by mutations in the MMAA or MMAB genes. To function properly, methylmalonyl CoA mutase must work together with the proteins made by these genes. Mutations that affect either of these proteins can impair the activity of methylmalonyl CoA mutase, leading to methylmalonic acidaemia.

Other genes that have not yet been identified may also cause methylmalonic acidaemia.

How do people inherit methylmalonic acidaemia?

This condition is inherited in an autosomal recessive pattern, which means two copies of a specific gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

What other names do people use for methylmalonic acidaemia?

• Methylmalonicacidaemia
• Methylmalonicaciduria
• Methylmalonic aciduria
• MMA