The MMUT gene encodes for the methylmalonyl-CoA mutase (MCM), a mitochondrial enzyme involved in the catabolism of some amino acids (valine, isoleucine, methionine and threonine) and other compounds such as the odd chain fatty acids and the cholesterol within the propionate pathway. MCM catalyzes the isomerization of L-methylmalonyl-CoA into succinyl-CoA before its entry in the tricarboxylic acid cycle. Defect in MCM is responsible for isolated methylmalonic academia (iMMA). Accumulation of methylmalonic acid (MMA) without homocysteine is the common hallmark of the typical iMMA that may also be due to mutations in the MMAA, MMAB and MMADHC genes.
Classical neonatal form of the disease is due to complete MCM deficiency and presents with acute signs of intoxication including vomiting, feeding difficulties, progressive neurological deterioration ranging from lethargy to coma, metabolic acido-ketosis, hyperammonemia and pancytopenia. Late onset forms can present at any age with a more heterogeneous clinical picture. The main complication of the disease is a progressive kidney disease leading to chronic renal insufficiency and kidney transplantation.
iMMA prevalence is estimated around 1/50 000.
All the iMMA are transmitted in an autosomal recessive mode.