A rare case of prolidase deficiency with situs inversus totalis, identified by a novel mutation in the PEPD gene

Clinical Genetics of Prolidase Deficiency: An Updated Review

“…Developmental delay or intellectual disability (moderate, mild or severe) was present in 71% (48/68) patients (Figure 1a). Nevertheless, 20 patients aged from four to 47 were reported without any delay [4,10,16,18,22,28,30,[32][33][34][35][36][37], two had normalized their previous developmental delay [16,38], three patients had speech delay [10,18] and one had motor delay with normal intellectual development [16] (Table S1). The expression of developmental delay may vary among siblings [16,35], suggesting that other factors play a role in the severity of the phenotype.…”

“…The histological analysis mainly focused on the patient's skin surrounding the ulcers. The reported dermatological lesions were leukocytoclastic vasculitis [10] and nonspecific inflammatory changes [36]. Deposition of amorphous substance was also described as resembling amyloid fibrils in the vicinity of capillaries.…”

Obstinate leg ulceration secondary to prolidase deficiency, treated with 5% topical proline

“…The enzyme works by cleaving iminodipeptides into proline and hydroxyproline, which are integral parts of collagen maintenance. A deficiency in prolidase leads to high circulating volumes of iminodipeptides and subsequent urinary excretion 2 …”

“…Prolidase deficiency (PD) is a rare autosomal recessive genodermatosis, with less than 100 cases reported in the literature 1 . PD is caused by biallelic variants in the prolidase D ( PEPD ) gene 2 . At least 30 pathogenic (or likely pathogenic) variants have been reported to date on ClinVar (https://www.ncbi.nlm.nih.gov/clinvar), a database of human variation.…”

PROLIDASE: A Review from Discovery to its Role in Health and Disease

“…A single nucleotide base substitution of C to T at position 551 in exon 8 of PEPD gene was identified in a PD patient, that yielded a stop codon instead of arginine, resulting in a 20 kDa defective prolidase (Kikuchi et al, 2000). Recently, a single nucleotide deletion, causing a frameshift mutation and encoding a premature stop codon in the PEPD gene was reported to disrupt the enzymatic function of prolidase (Kiratli Nalbant et al, 2019). Likewise, another study reported a homozygous nonsense variation in exon 5 of the PEPD gene that resulted in a stop codon and premature truncation of the protein at codon 140 resulting in PD (Chidambaram et al, 2021).…”