5‐OXOPROLINURIA DUE TO HEREDITARY 5‐OXOPROLINASE DEFICIENCY IN TWO BROTHERS–A NEW INBORN ERROR OF THE γ‐GLUTAMYL CYCLE

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Abstract
Two brothers, aged 16 and 11 yr, had recurrent episodes of vomiting, diarrhea and abdominal pain, starting in infancy. In spite of extensive investigations no cause of their enterocolitis could be established. After several years, symptomatic treatment was discontinured without any recurrence of symptoms. Their father and several paternal relatives have had kidney stones. Both boys developed urolithiasis and an oxalate-containing stone was removed from the elder brother''s kidney. He had no hypercalciuria. His glomerular and tubular function tests were normal. Gas chromatography of urine from both brothers revealed massive excretion of L-5-oxoproline (pyroglutamic acid). Glutathione levels in erythrocytes of both patients were normal. The activities of enzymes of the .gamma.-glutamyl cycle were analyzed in erythrocytes, leukocytes and cultured skin fibroblasts. The level of glutathione synthetase (EC 6.3.2.3) was normal, as was the affinity of this enzyme for its substrate .gamma.-glutamyl-cysteine. Feedback inhibition of .gamma.-glutamyl-cysteine synthetase (EC 6.3.2.2) by glutathione was also normal. Both patients had a specific deficiency of 5-oxoprolinase (EC 3.5.2.9), the activity of which was 2-4% of that of control subjects. Their parents had intermediate 5-oxoprolinase activities in fibroblasts, indicating a recessive mode of inheritance. Thus, 5-oxoprolinuria in these 2 patients was due to a lack of 5-oxoprolinase, i.e., a new inborn error in the .gamma.-glutamyl cycle.

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