Beyond Dermatological Findings: Multisystem Involvement in Prolidase Deficiency

Abstract

Objective: Prolidase deficiency is a metabolic and immunological disorder that is inherited in an autosomal recessive manner. In prolidase deficiency, a broad spectrum of differences is observed in patients, ranging from asymptomatic to multisystem involvement. There is scarce information in the literature on the atypical features and immunophenotypes of this disease. Aim of this study is to present 4 new cases to provide information on the rare features of the disease and to raise awareness. Materials and Methods: This study included 4 female patients with prolidase deficiency. Their demographic, clinical, and immunologic characteristics were obtained from their medical records. Results: There were 4 female patients (P1-P4), with a mean age of 18.5 years (min-max: 10-29) and a mean age of symptom onset of 6.9 years (min-max: 0.04-27). The main presenting complaints of the patients were skin lesions (100%), dysmorphic features (100%), neurodevelopmental delay (100%), frequent infections (100%), and prolonged diarrhea (50%). P2 had diffuse large B-cell lymphoma, resulting in early death. Interestingly, P1 and P2 experienced opportunistic infections such as cytomegalovirus, Epstein-Barr virus, and Pneumocystis jirovecii. Three patients (75%) had lymphopenia. Two patients had elevated IgE levels. Lymphocyte subgroup analysis showed an inverted CD4/CD8 ratio in all patients. In patients P1 and P2, the percentages of naive T cells and recent thymic emigrants were reduced, suggesting combined immune deficiency at the time of diagnosis. CD19+ B cells were also low in P1 and P2. Metabolic evaluations revealed low prolidase enzyme activity in P1 and P2. Conclusion: Beyond the well-known classical dermatological findings, the presence of recurrent opportunistic infections, gastrointestinal involvement, malignancy, and flow cytometry findings suggestive of combined immunodeficiency indicate that the diagnosis of prolidase deficiency may be underestimated. Knowing the atypical and rare presentations will facilitate diagnosis and treatment of affected patients.

Figure 1.

Common clinical findings and laboratory results in prolidase deficiency.

Figure 2.

Abnormal clinical phenotypes in prolidase deficiency. Patients exhibit various facial dysmorphisms. In P1, these include a prominent forehead, hypertelorism, ptosis, ocular proptosis, exophthalmos, upslanting palpebral fissures, a small nose, a low nasal root, and a slender upper lip. In P2, observed features include a prominent forehead, down slanting palpebral fissures, a low nasal root, and a beaked nose.

Figure 3.

Clinical phenotypes of patients with PEPD deficiency, highlighting specific features. Skin lesions commonly observed in prolidase deficiency, particularly on the anterior surface of the tibia (P2). Left panel: Circinate, erythematous, scaly patches with active borders (potassium hydroxide mount positive). Middle panel: A scaly patch in the pretibial area that has ulcerated. The borders remain active, resembling tinea corporis. A punch biopsy from the ulcer border revealed fungal hyphae. Right panel: Hemorrhagic blisters at the pretibial site that progressed into deep ulcers. Multiple ulcers developed in the same area during follow-up.

Figure 4.

Radiological findings of patients with PEPD deficiency. Hepatosplenomegaly and atelectatic lung areas in P1. Diffuse ground-glass opacities during Pneumocystis jirovecii pneumonia in P2, with more prominent pleural effusion in the right lung. White arrows indicate the abnormalities.