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Prolidase deficiency
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Prolidase deficiency

Prolidase deficiency is a rare, inherited disorder that affects the body's ability to recycle proline, leading to skin lesions, intellectual disability, and immune system susceptibility.

Overview

Prolidase deficiency is a disorder that typically becomes apparent during infancy. It is characterized by a wide variety of symptoms, including organ enlargement, skin issues, and developmental delays.

Symptoms

  • Organ Involvement: Enlargement of the spleen (splenomegaly) or both the spleen and liver (hepatosplenomegaly).
  • Digestive and Respiratory Issues: Diarrhea, vomiting, dehydration, and susceptibility to severe skin, ear, or respiratory tract infections. Some individuals develop chronic lung disease.
  • Facial Features: Prominent, widely spaced eyes (hypertelorism), high forehead, flat nasal bridge, and a small lower jaw (micrognathia).
  • Developmental Delays: Approximately 75 percent of affected individuals have intellectual disability ranging from mild to severe.
  • Skin Lesions: Rashes or severe skin ulcers, particularly on the hands, feet, lower legs, and face. These ulcers may not heal completely, leading to complications like infection or amputation.

Causes

Prolidase deficiency is caused by mutations in the PEPD gene, which provides instructions for making the enzyme prolidase. This enzyme is responsible for breaking down dipeptides containing the amino acids proline or hydroxyproline. Prolidase is essential for recycling these amino acids for protein production and for the breakdown of collagens, which support tissues like skin, bone, and cartilage. The loss of prolidase activity leads to an accumulation of undigested dipeptides, which may cause cell death, inflammation, and the characteristic skin and developmental symptoms.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the PEPD gene in each cell have mutations. Parents of an affected individual each carry one copy of the mutated gene but typically do not show signs of the condition.

Frequently Asked Questions

While no diet can replace the missing enzyme, a protein‑restricted diet low in proline‑rich foods (e.g., gelatin, collagen supplements) may lessen peptide accumulation. Some clinicians trial oral proline or glycine supplementation to support collagen synthesis, but evidence is limited; supplementation should be guided by a metabolic specialist and monitored for renal function and amino‑acid balance.
Because the disorder is autosomal recessive, each sibling has a 25 % chance of being affected, a 50 % chance of being an asymptomatic carrier, and a 25 % chance of being unaffected and non‑carrier. Carrier testing for parents and at‑risk relatives is recommended, and couples can consider prenatal diagnosis (chorionic villus sampling or amniocentesis) or pre‑implantation genetic testing in future pregnancies to avoid recurrence.
Prolidase‑deficiency ulcers are typically chronic, deep, and located on the dorsal hands, feet, lower legs, and face, often with a chalky or hyperkeratotic border and poor healing despite standard wound care. Biopsy shows collagen degeneration and accumulation of imidodipeptides, and a definitive diagnosis is confirmed by low plasma prolidase activity and pathogenic PEPD mutations, which distinguishes it from conditions like pyoderma gangrenosum or vasculitis.
Patients often have combined immunodeficiency; regular immunoglobulin replacement (IVIG or subcutaneous) is recommended when IgG levels are low or infections are frequent. Prophylactic antibiotics (e.g., trimethoprim‑sulfamethoxazole) can prevent opportunistic bacterial infections, and annual influenza vaccination plus pneumococcal vaccination (non‑live formulations) are advised. Prompt treatment of skin ulcer infections with culture‑directed antibiotics is essential to avoid sepsis.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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