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At a glance

A rare congenital disorder of the small peptides metabolism (imidazoles dipeptides). It is characterized by mild to severe skin lesions (mostly the face, palms, lower legs, and soles), cognitive impairment, splenomegaly, recurrent infections involving mainly the respiratory system, and iminodipeptiduria.


Imidodipeptidase; Peptidase D; Proline Dipeptidase; Hyperiminodipeptiduria.


Estimated to be 1 to 2:1,000,000. Higher in some populations such as Amish people.

Genetic inheritance

Autosomal recessive.


Prolidase deficiency is caused by mutations of the PEPD gene which maps to chromosome 19p13.2. The exopeptidase prolidase hydrolyzes dipeptides that have either carboxy-terminal proline or hydroxyproline. The deficiency in prolidase produces massive excretion of imidopeptides (ie, dipeptides with a proline or hydroxyproline N-terminal). Prolidase deficiency also seems to be a risk factor for the development of systemic lupus erythematosus.


Hyperiminopeptiduria; low or absent prolidase activity in leukocytes or fibroblasts.

Clinical aspects

First symptoms appear between birth and 22 years of age; prognosis, age of onset, and severity of the lesions are highly variable: skin lesions: rash with diffuse telangiectasia, ecchymosis, difficult to cure leg ulcers; characteristic facies: prominent skull sutures, ptosis and proptosis; recurrent (necrotic) infections of the skin, chronic ear and sinus infections; impaired motor or cognitive development may be present. Treatment: Oral ascorbate or manganese and steroids are useful for the treatment of skin lesions.

Precautions before anesthesia

Presence of foci of chronic infection. Check full blood count in the presence of hypersplenism.

Anesthetic considerations

Careful positioning because of fragile skin and the presence of ulcers.

Pharmacological implications

There are no known pharmacological implications.


Larsson  A, Jaeken  J: Disorders in the metabolism of glutathione and imidazole peptides, in Fernandes  J, Saudubray  JM, Van den Bergh  G (eds): Inborn Metabolic Diseases, 3rd ed. Berlin, Springer, 2000, p 312.
Nir  V, Ilivitky  A, Hakim  F,  et al: Pulmonary manifestations of prolidase deficiency. Pediatr Pulmonol 51:1229, 2016.  [PubMed: 27132891]

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