Type II hyperprolinemia. Δ¹ Pyrroline 5 carboxylic acid dehydrogenase deficiency in cultured skin fibroblasts and circulating lymphocytes

Type II hyperprolinemia is an inherited abnormality in amino acid metabolim characterized by elevated plasma proline concentrations, iminoglycinuria, and the urinary excretion of Δ¹ pyrroline compounds. To define the enzymologic defect of this biochemical disorder, a specific, sensitive radioisotopic assay was developed for the proline degradative enzyme Δ¹ pyrroline 5 carboxylic acid dehydrogenase. Using this assay, an absence of Δ¹ pyrroline 5 carboxylic acid dehydrogenase activity was demonstrated in the cultured fibroblasts from 3 patients with type II hyperprolinemia. This result was confirmed on cultured cells by demonstrating a similar absence of Δ¹ pyrroline 5 carboxylic acid dehydrogenase activity in extracts prepared from the peripheral leukocytes of these patients. Additionally, the authors significantly decreased levels of Δ¹ pyrroline 5 carboxylic acid dehydrogenase activity in the leukocyte extracts from 5 obligate heterozygotes for type II hyperprolinemia. The authors also demonstrated a reduction in leukocyte Δ¹ pyrroline 5 carboxylic acid dehydrogenase activity in 3 successive generations of a family. These results prove that an absence of Δ¹ pyrroline 5 carboxylic acid dehydrogenase is the enzymologic defect in type II hyperprolinemia and that this defect is inherited in an autosomal recessive fashion.