Prolidase deficiency: its dermatological manifestations and some additional biochemical studies

Abstract

Prolidase deficiency occurred in a 13-year-old girl. Determinations were made of prolidase and prolinase activities in cultured fibroblasts, and thin layer chromatographic studies of skin prolidase were performed. The patient had chronic, recurrent ulcers on the legs and feet, diffuse telangiectasia, shallow scar-like atrophic lesions on the face and arms, soft and thin abdominal skin, and premature gray hairs. Prolidase in the patient's skin fibroblasts was absent. Greatly reduced prolidase activity was demonstrated in the patient's skin. A review of hitherto reported cases of this disease showed such skin manifestations as (1) skin ulceration or skin fragility with scar formation, (2) purpuric lesions, (3) telangiectasia and/or photosensitivity, and (4) thickening of the skin with lymphedema.

Amelioration of prolidase deficiency in fibroblasts using adenovirus mediated gene transfer

“…Cultured skin fibroblasts were obtained from two Japanese female siblings with prolidase deficiency. Clinical features (Arata et al, 1979) and a molecular defect in these patients have been described previously (Tanoue et aL, 1990). Normal and affected human skin fibroblasts and human embryonic kidney 293 cells were maintained in Dulbecco's modifed Eagle's medium (DMEM), supplemented with 10% heat-inactivated fetal calf serum, penicillin, and streptomycin at 37°C in 5% CO2.…”

Prolidase Directly Binds and Activates Epidermal Growth Factor Receptor and Stimulates Downstream Signaling

“…PEPD-deficient patients present massive urinary elimination of iminodipeptides (44,45) and show a wide range of clinical outcome, such as intractable skin ulcer, recurrent infection, and mental retardation (46 -48). The disease mechanism of PEPD deficiency remains poorly understood.…”

Studies on prolidase deficiency with a possible defect in collagen metabolism.

“…13.9, proline dipeptidase) with imidodipeptiduria. There have been reported at least eight cases of proven or highly suspected cases of prolidase deficiency as summarized by Scriver (1978) and by Arata et al (1979). In spite of the description of the first case of this disease as a syndrome resembling lathyrism (Goodman et al 1968) and the suggestion of abnormal collagen metabolism in these patients (Jackson et al 1975), few direct analyses of collagen and its metabolites of patients have been performed (Goodman et al 1968;Isemura et al 1979).…”

“…The role of prolidase deficiency in the skin pathology has not been clearly defined. Since the disease accompanies hyperimidodipeptiduria, the defect in collagen metabolism caused by continuous loss of proline has been suggested to account for the pathogenesis (Jackson et al 1975;Arata et al 1979). In spite of this suggestion, amino acid analyses of patient's skin collagens have failed to reveal any significant difference from normal samples (Goodman et al 1968;Isemura et al 1979).…”

“…It has been puzzling that there are cases of prolidase deficient persons with hyperimidodipeptiduria yet without clinical symptoms (Arata et al 1979;Isemura et al 1979). In our case, onset of the disease was at 8 years of age and her prolidase deficient brother is asymptomatic even at 26 years of age.…”