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Diseases

Genetic and Rare Diseases Information Center (GARD)

Prolidase deficiency


Other Names for this Disease
  • Hyperimidodipeptiduria
  • Imidodipeptidase deficiency
  • Peptidase deficiency
  • PD
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I have prolidase deficiency and would like to receive as much information as possible as well as contact other sufferers.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

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).[1][2][3] Symptoms typically present during infancy and vary greatly among affected individuals.[2] The condition is caused by mutations in the PEPD gene. It is inherited in an autosomal recessive pattern.[1][2][3] Treatment for prolidase deficiency is symptomatic and supportive and often requires the expertise of a multidisciplinary team.[1]
Last updated: 3/25/2016

What are the signs and symptoms of prolidase deficiency?

Prolidase deficiency can cause a wide variety of symptoms. In most cases, symptoms first present during infancy.[2] Affected individuals may have an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly) with elevated liver enzymes, or an enlarged liver and spleen (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency are susceptible to skin lesions on their hands, feet, lower legs and face. The severity of the skin involvement may range from a mild rash to severe skin ulcers that are difficult to treat. Recurrent infections of the respiratory tract can also occur. Characteristic facial features in people with prolidase deficiency include prominent eyes that are widely spaced (hypertelorism), a high forehead, a flat bridge of the nose, and a very small lower jaw and chin (micrognathia). Some children may experience delayed development and intellectual disability.[2][1] Laboratory tests may show a high level of imidodipeptides (a type of protein) in the urine, anemia, thrombocytopenia, hypergammaglobulinemia (high levels of antibodies in the blood), and hypocomplementemia (abnormally low complement levels in the blood).[2][1][3] Some people with prolidase deficiency do not have any symptoms. In these individuals, the condition can be detected through newborn screening or testing following the diagnosis in a relative.[2] An association between prolidase deficiency and systemic lupus erythematous has been reported.[1] 
Last updated: 3/25/2016

What causes prolidase deficiency?

Prolidase deficiency is caused by mutations in the PEPD gene.[1][2][3] 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.[2]

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.[2]

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.[2]
Last updated: 3/25/2016

Is prolidase deficiency an inherited condition?

Yes. Prolidase deficiency is inherited in an autosomal recessive manner.[1][2][3] 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).[2] 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: 3/25/2016

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.[1]
Last updated: 3/25/2016

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: 3/25/2016

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: 3/25/2016

References
Other Names for this Disease
  • Hyperimidodipeptiduria
  • Imidodipeptidase deficiency
  • Peptidase deficiency
  • PD
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.