cblB Type Methylmalonic aciduria

Within the group of methylmalonic acidurias dependent on vitamin B12 (or cobalamin), which is characterized by the fact that patients usually respond to treatment with vitamin B12, we find methylmalonic acidemia type cblB.

Methylmalonic aciduria type cblA (which is studied in another item in this section on hereditary conditions) is caused by defects in the MMAA gene, whereas methylmalonic aciduria type cblB is caused by alterations in the MMAB gene, which codes for a coenzyme that interacts with the mitochondrial enzyme methylmalonyl-CoA mutase (mut). The mut enzyme plays an essential role in the metabolism of proteins, lipids and cholesterol.

Symptoms of methylmalonic acidemia cblB usually appear between the first year of life and 14 years of age. An accumulation of methylmalonic acid occurs in blood and urine causing these fluids to become more acidic (acidemia). Patients may present with lethargy, failure to thrive, recurrent vomiting, dehydration, respiratory distress and hypotonia, anemia, intellectual deficit and are prone to life-threatening acidic crises.

It may have a late onset and course with ataxia, dementia and psychosis. In 66% of cases it can lead to chronic kidney disease.

The diagnosis of methylmalonic aciduria is based on biochemical tests. Increased production of methylmalonic acid and its metabolites is detected by chromatography in urine and/or blood samples. In many countries this pathology is included in newborn screening. In addition, it is often combined with analysis of mutations and/or enzyme activity to profile the type of methylmalonic acidemia involved. Defining the type of aciduria is important because mut-, cblA and cblB forms have a better prognosis and evolution.

Patients with methylmalonic aciduria type cblB can be treated with hydroxocobalamin to decrease methylmalonic acid levels in body fluids, but only in those cases that respond to treatment.