Prolidase deficiency: biochemical study of erythrocyte and skin fibroblast prolidase activity in Italian patients.
METHODS
Prolidase deficiency (PD), a rare, autosomally inherited disorder causing iminodipeptiduria is associated with a number of clinical manifestations, the principle feature being chronic skin ulceration. The enzyme prolidase cleaves iminodipeptides containing C-terminal prolyl or hydroxyprolyl residues and is important in the final stages of protein catabolism. We report clinical and biochemical findings in 8 Italian patients with proven prolidase deficiency. There was considerable heterogeneity in age at onset of symptoms (varying from 3-17 years), mental retardation and clinical manifestations (asymptomless to very severe). Prolidase activity was determined in hemolysates of patient erythrocytes and cultured dermal fibroblasts.


RESULTS
Prolidase activity was found to be deficient, especially against gly-pro. Erythrocyte and fibroblast enzyme was also separated into two forms, a major isoform (I) and a minor one (II) by fast protein liquid chromatography, and activity against different iminodipeptide substrates was tested. Isoform I activity was markedly reduced in all patients as compared to normal controls, while isoform II activity appeared to be unaltered.


CONCLUSIONS
We were unable to find any correlation between degree of enzyme activity loss and severity of symptoms.
Zanaboni
G
G
Centro per lo Studio delle Malattie del Tessuto Connettivo, Department of Biochemistry, University of Pavia, Italy.
Dyne
K M
KM
Rossi
A
A
Monafo
V
V
Cetta
G
G
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004150:Dipeptidases / Q000172:deficiency* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004151:Dipeptides / Q000652:urine; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology* / Q000235:genetics / Q000652:urine; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D007558:Italy; D008297:Male; D011392:Proline / Q000378:metabolism; D012867:Skin / Q000201:enzymology / Q000473:pathology; D012883:Skin Ulcer / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D013379:Substrate Specificity; D013684:Telangiectasis / Q000201:enzymology* / Q000235:genetics
D004151:Dipeptides; D007527:Isoenzymes; D011392:Proline; D004150:Dipeptidases; C022449:proline dipeptidase