What is methylmalonic acidemia?

Methylmalonic acidemia is a congenital anomaly that affects the metabolism of vitamin B12. The body can not break down certain proteins and fats, resulting in the accumulation of methylmalonic acid in the blood.

The disease is usually diagnosed in the first year of life. Approximately 1 in every 25,000 to 48,000 babies are born with this condition. The symptoms are evident during childhood and vary from one person to another.

Causes of methylmalonic acidemia

The cause of methylmalonic acidemia sensitive to vitmin B12 is a defect in the synthesis of the adenosyl-cobalamin cofactor (AdoCbl) due to genetic alterations in the genes MMAA (4q31.1-2), MMAB (12q24.1) and MMADHC (2q23.2).

Methylmalonic acidemia resistant to vitamin B12 is caused by a complete or partial deficit in the activity of the enzyme mitochondrial methylmalonyl-Coa mutase. However, in this case, the mutations are in the MUT gene (6p21).

However, all methylmalonic acidemias are transmitted following a autosomal recessive inheritance pattern.


The signs and symptoms of methylmalonic acidemia can include vomiting, dehydration, hypotonia, developmental delay, fatigue, and hepatomegaly. On the other hand, in the long term, complications can appear among which are:

If the affected people do not receive treatment, they may go into a coma or even die. Those affected with isolated methylmalonic acidemia may have the following symptoms depending on the form of the disease:

Infant form

It is the enzymatic subtype resistant to vitamin B12, and It is the most common form of isolated methylmalonic acidemia. It occurs during childhood. Children are normal at birth, however, they quickly manifest symptoms such as lethargy, vomiting and dehydration.

Then, liver enlargement, hypotonia, and encephalopathy become evident. At the level of analysis in the laboratory, The following parameters are measured:

  • Ketosis and ketonuria.
  • Ammonium in blood.
  • Severe metabolic acidosis
  • Increase of glycine in blood.

Read also: Everything you need to know about vitamin B12

Partially deficient form

It is the form sensitive to vitamin B12 and occurs in the first months or years of life. Affected children may have feeding problems such as anorexia vomiting, hypotonia, and developmental delay.

In some cases, after ingesting proteins, there may be vomiting. Children affected by this form of methylmalonic acidemia are at risk of metabolic decompensation, so it is very important to diagnose and start treatment as soon as possible.

Usually, until the first episode of vomiting, dehydration, lethargy or coma occurs it is not known that the person suffers from this metabolic alteration.

Benign form or adult form

The affected people have been considered as stable, but they may be prone to acute metabolic decompensation. The cause of this type of methylmalonic acidemia has not been fully established.

Treatment of methylmalonic acidemia

The treatment must be started immediately after having the diagnosis. The sooner the treatment begins, the better the patient's evolution will be.

Nowadays, Diet is the basis of treatment for methylmalonic acidemia. Dietary treatment aims to prevent the accumulation of substrates and metabolites associated with toxic levels.

The treatments recommended for children with methylmalonic acidemia are:

  • L-carnitine: This substance, besides being safe and natural, helps the body to produce energy and eliminate waste.
  • Oral antibiotics: these drugs can help reduce the amount of methylmalonic acid in the intestine.
  • Vitamin B12 injections: more than 90% of cases with CblA deficiency respond to this treatment. In addition, it helps 40% of children with CblB deficiency.

In case there are symptoms of a metabolic crisis, you should go to the hospital. Hospital treatment includes intravenous bicarbonate to reduce the acidity of the blood.

Further, intravenous glucose is usually administered to prevent the breakdown of protein and stored fat in the body.

You may also be interested: Symptoms that you have vitamin B12 deficiency


It is recommended a dietary regimen low in amino acids and with limited amounts of protein. The diet will consist, mainly, of carbohydrates such as cereals, fruits, pasta and vegetables.

People suffering from this condition should avoid contact with people suffering from contagious diseases such as colds or flu, to avoid complications.