ABSTRACT
A patient with propionic acidemia was reported in 1961 [1] as having hyperglycinemia, a disorder of amino acid metabolism. Its most prominent feature was recurrent attacks of ketoacidosis. Analysis of the amino acids of blood and urine revealed very large quantities of glycine. Attacks were related to the intake of protein, and it was shown that ketonuria resulted regularly from the administration not of glycine, but of branched-chain amino acids and threonine and methionine [1,2]. The discovery of a group of patients with hyperglycinemia who had none of these characteristics led us to the term nonketotic hyperglycinemia (Chapter 27, p. 183) to distinguish them from the original group that we called ketotic hyperglycinemia. The discovery of methylmalonic acidemia in a
group of patients who displayed the ketotic hyperglycinemia syndrome [3,4,5] led initially to the thought that all these patients had methylmalonic acidemia. However, study of our initial patient and his sister, by Rosenberg and colleagues [6], indicated that neither excreted methylmalonic acid, and that they had propionic acidemia as a result of defective activity of propionyl CoA carboxylase (Figure 2.1). This enzyme is the first step in the pathway of propionate metabolism in which propionyl CoA, the product of the metabolism of isoleucine, valine, threonine and methionine is converted to methylmalonyl CoA acid, then to succinyl CoA and oxidation in the citric acid cycle.
