Al-PYRROLINE-5-CARBOXYLIC ACID DEHYDROGENASE DEFICIENCY IN CULTURED SKIN FIBROBLASTS AND CIRCULATING LYMPHOCYTES

abnormality in amino acid metabolism characterized by elevated plasma proline concentrations, iminoglycinuria. and the urinary excretion of A1-pyrroline compounds. To define the enzymologic defect of this biochemical disorder, we developed a specific, sensitive radioisotopic assay for the proline degradative enzyme A'-pyrroline-5carboxylic acid dehydrogenase. Using this assay, we have shown an absence of A'-pyrroline-5-carboxylic acid delhydrogenase activity in the cultured fibroblasts from three patients with type II hyperprolinemia. \Ve confirmed this result on cultured cells by demonstrating a similar absence of Al-pyrroline-5-carboxylic acid dehydrogenase activity in extracts prepared from the peripheral leukocytes of these patients. Additionally, we found significantly decreased levels of A'-pyrroline-5-carboxylic acid dehlvdrogenase activity in the leukocyte extracts from five obligate heterozygotes for type II hyperprolinemia. We also demonstrated a reduction in leukocyte AL-pyrroline-5-carboxylic acid dehydrogenase activity in three successive generations of a family. A portion of this work was presented at the Annual Meeting of The Society for Pediatric Research in Washiilgton, D. C., 3 May 1974, and at the National Meeting of The American Society for Clinical Investigation in Atlantic City, N. J., 3 'May 1975. Received for puiblicationt 12 Decemizber 1975 antd ini revised formii 23 April 1976. These results prove that an absence of A'-pyrroline-5carboxylic acid dehydrogenase is the enzymologic defect in type II hyperprolinemia and that this defect is inherited in an autosomal recessive fashion.