Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency

Vitamin B12-unresponsive methylmalonic acidemia type mut-, or methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency, is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.

The prevalence of this form of the disease is unknown but to date have reported more than 450 cases.

The disease is caused by partial deficiency in the activity of the mitochondrial vitamin B12-dependent enzyme methylmalonyl-CoA mutase which is a result of mutations in the MUT gene (6p21). It is transmitted as an autosomal recessive trait.

The disease usually occurs in the first weeks of life, although cases of later onset have been described, clinical manifestations include lethargy, failure to thrive, recurrent vomiting, dehydration, respiratory distress, muscle hypotonia, developmental delay, intellectual deficit, hepatomegaly and coma. Patients may show signs of anemia. They may also have potentially life-threatening ketoacidosis or hyperammonemia, renal and neurological complications, metabolic stroke and cardiomyopathy.

Vitamin B12-unresponsive methylmalonic acidemia type mut- is generally less severe than vitamin B12-unresponsive methylmalonic acidemia type mut0, and may in some cases respond to vitamin B12 therapy.

Long term complications include metabolic stroke and development of end stage renal failure. These complications are more frequent in mut0 than in mut-.

Gene or region studied

  • MUT
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