Prolidase deficiency

What causes prolidase deficiency?

Prolidase deficiency is caused by mutations in the PEPD gene. This gene provides instructions for making the enzyme prolidase, also called peptidase D. Prolidase helps divide certain dipeptides, which are molecules composed of two protein building blocks (amino acids). More specifically, prolidase divides dipeptides containing the amino acids proline or hydroxyproline. By freeing these amino acids, prolidase helps make them available for use in producing proteins that the body needs.

Prolidase is also involved in the final steps of the breakdown of some proteins obtained through the diet and proteins that are no longer needed in the body. Prolidase is particularly important in the breakdown of collagens, a family of proteins that are rich in proline and hydroxyproline. Collagens are an important part of the extracellular matrix, which is the lattice of proteins and other molecules outside the cell. The extracellular matrix strengthens and supports connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Collagen breakdown occurs during the maintenance (remodeling) of the extracellular matrix.

PEPD gene mutations that cause prolidase deficiency result in the loss of prolidase enzyme activity. It is not well understood how the absence of prolidase activity causes the various signs and symptoms of prolidase deficiency.

Last updated on 05-01-20

How is prolidase deficiency diagnosed?

The diagnosis of prolidase deficiency is based on the presence of characteristic clinical symptoms, high levels of imidodipeptides in the urine, and detection of either mutations in the PEPD gene or reduced levels of prolidase enzyme activity.

Last updated on 05-01-20

Is prolidase deficiency inherited?

Prolidase deficiency is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the PEPD gene in each cell. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition (carriers). When 2 carriers of an autosomal recessive condition have children, each child has a:

  • 25% (1 in 4) chance to be affected,
  • 50% (1 in 2) chance to be an unaffected carrier like each parent,
  • 25% (1 in 4) chance to be unaffected and not be a carrier.

Last updated on 05-01-20

What is prolidase deficiency?

Prolidase deficiency is a rare metabolic condition characterized by skin lesions, recurrent infections, unusual facial features, variable intellectual disability, enlargement of the liver (hepatomegaly) with elevated liver enzymes, and enlargement of the spleen (splenomegaly). Symptoms typically present during infancy and vary greatly among affected individuals. The condition is caused by mutations in the PEPD gene. It is inherited in an autosomal recessive pattern. Treatment for prolidase deficiency is symptomatic and supportive and often requires the expertise of a multidisciplinary team.

Last updated on 05-01-20

Are there any support groups for prolidase deficiency?

We were unable to find a support group specifically for prolidase deficiency. According to the medical literature review, approximately 90 cases have been reported. There is an organization based in the United Kingdom called Children Living with Inherited Metabolic Diseases (CLIMB) that lists prolidase as a supported inherited metabolic disease.

Last updated on 05-01-20

What is the long-term outlook for people with prolidase deficiency?

The long-term outlook can vary because of the large possible range of severity in each person. For example, while skin ulcers lead to amputations in some people, others continue to be symptom-free.

In most cases, people with prolidase deficiency experience a reduced quality of life because of infections and chronic pulmonary (lung) complications. Life expectancy is often decreased, with infection being the most common cause of death.

Last updated on 05-01-20

How might prolidase deficiency be treated?

There is no cure for prolidase deficiency. Treatment is aimed at treating the specific symptoms present in each individual. A multidisciplinary team of specialists is often needed. Supportive treatment of the skin, lung, and immunologic manifestations has been helpful in some cases. Further details related to treatments that have been tried in these patients can be accessed here.

Last updated on 05-01-20

Name: Metabolic Support UK 5 Hilliards Court Sandpiper Way
Chester Business Park
Chester, CH4 9QP, United Kingdom
Phone: 0845 241 2173 Toll Free: 0800 652 3181 Email: Url:

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