A prolidase deficiency diagnosis often requires a high index of suspicion due to its multisystemic nature. This rare autosomal recessive metabolic disorder stems from mutations in the PEPD gene. Consequently, it impairs collagen turnover and presents with recurrent ulcerative skin lesions. Moreover, patients frequently suffer from recurrent infections and hematological abnormalities like pancytopenia. Recently, a case report highlighted an 18-year-old Indian male with lifelong skin ulcers and chronic diarrhea. Furthermore, his diagnostic journey involved a complex clinical overlap with celiac disease.

Establishing a Prolidase Deficiency Diagnosis via Genetic Testing

Initially, clinicians diagnosed the patient with iron deficiency anemia and celiac disease at age 15. Investigations revealed raised anti-tissue transglutaminase antibodies and villous atrophy. However, his symptoms persisted despite a strict gluten-free diet. Therefore, the medical team performed clinical exome sequencing to explore underlying causes. This identified a homozygous pathogenic splice site mutation (c.504-2A>G) in the PEPD gene. Thus, they established a definitive prolidase deficiency diagnosis. This underscores the necessity of genetic testing in refractory cases presenting with overlapping features.

Multidisciplinary Management and Clinical Outcomes

The management of this condition involves a comprehensive multidisciplinary approach. Firstly, the team initiated dietary modifications and iron supplementation to address the anemia. Additionally, they provided vitamin C and manganese, which are essential cofactors for collagen synthesis. Most importantly, the patient received oral L-proline powder to compensate for the enzymatic defect. Six months later, clinicians noted significant healing of the chronic skin ulcers. Furthermore, the patient's hematological parameters showed remarkable improvement. Early intervention and specific nutritional support remain vital for managing these rare metabolic disorders effectively.

Frequently Asked Questions

What are the primary symptoms of prolidase deficiency?

Common symptoms include chronic, nonhealing skin ulcers (mostly on lower limbs), recurrent respiratory infections, and dysmorphic facial features. Some patients also experience hematological issues like pancytopenia or splenomegaly.

How is this condition inherited?

Prolidase deficiency follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of the mutated PEPD gene, one from each parent, to develop the disorder.

Why is genetic testing important in these cases?

Since the condition can mimic other disorders like celiac disease or vasculitis, genetic testing provides a definitive diagnosis. It guides targeted therapy, such as L-proline supplementation, which can significantly improve clinical outcomes.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice or a professional relationship. It should not be used as a substitute for professional diagnosis and treatment. Refer to the latest local and national guidelines for clinical practice.

References

1. Gupta V et al. Challenging diagnosis: prolidase deficiency presenting as nonhealing ulcers and pancytopenia complicated by gluten enteropathy-a case report. J Med Case Rep. 2026 Apr 09. doi: 10.1186/s13256-026-05949-5. PMID: 41957649.


2. Spodenkiewicz M et al. Clinical genetics of prolidase deficiency: an updated review. Biology (Basel). 2020;9(5):108.


3. Hechtman P. Prolidase Deficiency. In: Adam MP et al., editors. GeneReviews®. University of Washington, Seattle; 1993–2024.