Methylmalonic acid (serum)

General Information

Methylmalonic acid is an intermediate product in the way of degradation (breakdown) of branched aliphatic amino acids - valine, isoleucine, threonine and methionine. The enzyme methylmalonyl-CoA mutase, whose coenzyme (activator) is a derivative of vitamin B12, participates in the metabolism of methylmalonic acid products.

Blockage of this metabolic pathway for any reason (including vitamin B12 deficiency) leads to the accumulation of methylmalonic acid and its toxic derivatives in the blood - methylmalonic acidemia.

Hereditary form

Methylmalonic acid is a marker of memkidar disease - methylmalonic acidemia. The incidence of this disease is 1:48000 live births. Half of the cases come from the deficiency of the enzyme - methylmalonyl-CoA-mutase. The disease is transmitted in an autosomal recessive manner. Such children have metabolic acidosis, muscle hypotonia, lethargy (pathological sleepiness), liver enlargement, chronic kidney damage, mental retardation. In severe cases, coma and shock develop in the first weeks of life.

purchased form

The acquired form of methylmalonic acidemia is more common. Malabsorption, malnutrition, vitamin B12 deficiency - ultimately lead to increased concentrations of methylmalonic acid in serum and urine. Elderly patients with vitamin B12 deficiency may present with peripheral neuropathies, ataxia, positional (proprioceptive) and vibrational (deep) sensitivity disorders, memory disorders, depression, and dementia—without developing anemia. Also, the determination of methylmalonic acid is considered an important marker in diagnosing vitamin B12 deficiency.

When should we do the research?

• When hereditary methylmalonic acidemia is suspected
• For the differential diagnostics of conditions associated with vitamin B12 deficiency.

Material for examination: Venous blood

Referral norms:  ​​ 9-32 ng/L (73-271 nmol/L) 

Interpretation of results

A significant increase in the serum level of methylmalone in children raises doubts about the genetic form of methylmalonic acidemia.

In adults – moderate elevations of methylmalonic acid are associated with B12 deficiency states.

Methylmalonic acidemia may develop with kidney failure, hypovolemia, and overgrowth of small intestinal microflora.