Pathophysiology In<unk> , the body is unable to break down the amino acids methionine, threonine, isoleucine and valine; as a result<unk>  acid builds up in the blood and tissues. Those afflicted with this disorder are either lacking functional copies or adequate levels of one or more of the following enzymes: methylmalonyl-CoA mutase, methylmalonyl-CoA epimerase, or those involved in adenosylcobalamin synthesis. Methylmalonyl-CoA mutase It is estimated that as many as 60% of cases are the result of a mutated MUT gene which encodes the protein methylmalonyl-CoA mutase. This enzyme is responsible for the digestion of potentially toxic derivatives of the breakdown of the above-mentioned amino acids and fats, primarily cholesterol, particularly this enzyme converts methylmalonyl-CoA into succinyl-CoA. Without this enzyme, the body has no means to neutralize or remove<unk>  acid and related compounds. The action of this enzyme can also be crippled by mutations in the<unk> A,<unk> B, and<unk> DHC genes, each of which encodes a protein required for normal functioning of methylmalonyl-CoA mutase. Methylmalonyl-CoA epimerase Mutations in the MCEE gene, which encodes the methylmalonyl-CoA epimerase protein, also referred to as methylmalonyl racemase, will cause a much more mild form of the disorder than the related methylmalonyl-CoA mutase variant. Like the mutase, the epimerase also functions in breaking down the same substances, but to a significantly lesser extent than the mutase does. The phenotypic differences caused by a deficiency of the epimerase as opposed to the mutase are so mild that there is debate within the medical community as to whether or not this genetic deficiency can be considered a disorder or clinical syndrome. Adenosylcobalamin Also known as vitamin B12, this form of cobalamin is a required cofactor of methylmalonyl-CoA mutase. Even with a functional version of the enzyme at physiologically normal levels, if B12 cannot be converted to this active form, the mutase will be unable to function. Progression Though there are not distinct stages of the disease,<unk>  is a progressive condition; the symptoms of this disorder are compounded as the concentration of<unk>  acid increases. If the triggering proteins and fats are not removed from the diet, this buildup can lead to irreparable kidney or liver damage and eventually death.
Methylmalonic acidemia
Hawkinsinuria
Phenylketonuria
Alkaptonuria
Glutaric acidemia type 2
Orotic aciduria
3-Methylglutaconic aciduria
Urocanic aciduria