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.
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