Prolidase Deficiency Causing Recalcitrant Leg Ulcerations in Siblings

Abstract

Prolidase deficiency (PD) is a rare autosomal recessive genodermatosis with variable clinical manifestations. It results from a mutation in the peptidase-D gene that leads to abnormal activity of the prolidase enzyme, an important player in collagen catabolism. The authors report the case of two siblings presenting with dysmorphic features, disturbed blood panel, and recalcitrant leg ulcerations of several years’ duration. Sequencing of the 15 exons and of the intron/exon junction regions of the peptidase-D gene revealed the presence of a homozygous pathogenic variant c.549-1G > A. An ointment with 5% proline and 5% glycine was compounded, and the patients were instructed to apply it once daily. A follow-up visit after 8 months revealed partial improvement of the ulcerations starting from the third month of treatment. These authors hope this case report sheds light on this disease and recommend it be incorporated into the differential diagnoses of chronic leg ulcerations, particularly those starting at a young age.

Cluster Case of Prolidase Deficiency: Varied Clinical Presentations and Management in a Sibling Trio

“…Clinically, PD is characterized by non-healing ulcers, distinctive facial features, intellectual impairment, hematological abnormalities, and splenomegaly, which are consistent with the presentation of our cases and two adult siblings from Lebanon with a long-standing history of the disease who were also children of consanguineous parents [3]. Recurrent ear infection was supported with the hearing loss in patient 1, but features, such as significant telangiectasias, thrombosis in the cutaneous microcirculation, or past history of respiratory infections, were not present, which were additional findings in a twins case of PD [4].…”

“…Management remains challenging, with varying treatment outcomes reported but no established practice guidelines. Topical proline and glycine ointments, immunomodulatory therapies, topical tacrolimus and steroids, hyperbaric oxygen therapy, and anticoagulant treatments have been attempted with delayed partial healing of wounds and halting progression of ulcers, but there is no definitive cure as ulcers recur after some time, ranging from a few months to a year [3][4][5][6][7][8].…”

“…A total of 175 cases have been reported worldwide, and only two individual cases have been reported in Pakistan [2]. There are no clinical practice guidelines for this condition, and it is managed symptomatically [3]. This case report describes a unique presentation of PD in three siblings, which has not been reported before, and discusses the clinical evaluation, diagnostic process, and tailored management, including three different treatment modalities with promising outcomes in challenging circumstances.…”

“…A total of 175 cases have been reported worldwide, and only two individual cases have been reported in Pakistan [ 2 ]. There are no clinical practice guidelines for this condition, and it is managed symptomatically [ 3 ].…”

Infections in Disorders of Immune Regulation

“…Laboratory findings often reveal elevated levels of immunoglobulins (IgG, IgA, IgM, and IgE), complement component C1q deficiency, and reduced levels of C3 and C4 complement components. Hypergammaglobulinemia may arise from recurrent infections or immune dysregulation [ 88 , 89 , 91 , 92 ]. The association between PD and SLE is marked by shared clinical manifestations such as anemia, thrombocytopenia, hypergammaglobulinemia, hypocomplementemia, and increased autoantibody titers.…”