Prolidase Deficiency

Review
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].

Excerpt

Clinical characteristics: Prolidase deficiency is characterized by skin lesions (typically severe, chronic, recalcitrant, and painful skin ulcers of the lower extremities and telangiectasias of the face and hands), recurrent infections (particularly of the skin and respiratory tract), dysmorphic facial features, variable intellectual disability, and organomegaly (typically splenomegaly but occasionally associated with hepatomegaly) with elevated liver enzymes. Skeletal anomalies, chronic pulmonary disease, anemia, thrombocytopenia, hypergammaglobulinemia, and hypocomplementemia are observed in a minority of affected individuals. An association between prolidase deficiency and autoimmune conditions – particularly systemic lupus erythematosus (SLE) – has been described.

Diagnosis/testing: The clinical diagnosis of prolidase deficiency can be established in a proband with characteristic clinical findings and imidodipeptiduria or reduced prolidase enzyme activity. The molecular diagnosis can be established in a proband with suggestive findings and biallelic pathogenic variants in PEPD identified by molecular genetic testing.

Management: Treatment of manifestations: Skin ulcers may require treatment by a wound care specialist; topical proline (often 5%) or topical 5% proline-5% glycine ointment applied with dressing changes has been successful in some affected individuals. Standard treatment for developmental delay / intellectual disability, seizures, infections, reactive airways disease / pulmonary hypertension, SLE-like features, hemophagocytic lymphohistiocytosis, mast cell activation, osteopenia, dental anomalies, and refractive errors. Anemia and thrombocytopenia rarely require treatment, but packed red blood cell or platelet transfusions may be considered in those with severe anemia or thrombocytopenia, respectively.

Surveillance: Measurement of growth parameters, monitoring for developmental progress and educational needs, assessment for new neurologic manifestations (changes in tone, seizures, movement disorders), monitoring for signs or symptoms of respiratory insufficiency, and assessment of mobility and self-help skills at each visit. Dental evaluation every six months after tooth eruption. Annual complete blood count, liver function tests, abdominal ultrasound to assess liver and spleen size, and skin examination for evidence of malignant transformation in persons with chronic recalcitrant skin ulcers. Ophthalmology evaluation annually or as clinically indicated.

Agents/circumstances to avoid: Individuals with prolidase deficiency who have splenomegaly should avoid contact sports given the increased risk for splenic rupture.

Genetic counseling: Prolidase deficiency is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for a pregnancy at increased risk are possible if the PEPD pathogenic variants in the family have been identified.

Publication types

  • Review