Methylmalonic acidemia is an inherited metabolic disorder thus far found in children and characterized by the excessive excretion of methylmalonate in the urine. Typically these children exhibit vomiting, lethargy, ketoacidosis, and failure to grow. Many of the patients are mentally retarded and die early in life. Two variants of this disease are known. In one, the administration of vitamin B12 will reverse or prevent these clinical findings, whereas in a second variant vitamin B12 therapy is of no value.This paper presents the first enzymatic evidence (obtained with cell-free liver extracts) that bears on two important aspects of the disease. It has been found that methylmalonylCoA carbonylmutase activity is essentially absent in the livers of patients suffering from one variant (vitamin B12-unresponsive) of the disease. Secondly, it has been found that the livers of patients with the second variant (vitamin B12-responsive) of the disease show normal enzymatic behavior in the presence of the coenzyme form of vitamin B12, but are identical to the vitamin B12-unresponsive variant in the absence of the added coenzyme. Thus the enzyme studies fully support the clinical observations that two types of this disease exist.
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