National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Prolidase deficiency


Other Names:
Hyperimidodipeptiduria; Imidodipeptidase deficiency; Peptidase deficiency; Hyperimidodipeptiduria; Imidodipeptidase deficiency; Peptidase deficiency; PD See More
Categories:
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
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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 53 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Abnormality of the hip bone
Abnormality of the hips
0003272
Abnormality of the middle ear 0000370
Carious teeth
Dental cavities
Tooth cavities
Tooth decay
[ more ] 		0000670
Crusting erythematous dermatitis 0007473
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity
[ more ] 		0000992
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root
[ more ] 		0005280
Dry skin 0000958
Erythema 0010783
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Palmoplantar keratoderma
Thickening of palms and soles
0000982
Papule 0200034
Pruritus
Itching
Itchy skin
Skin itching
[ more ] 		0000989
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
Skin ulcer
Open skin sore
0200042
Thin skin 0000963
30%-79% of people have these symptoms
Abnormal fingernail morphology
Abnormal fingernails
Abnormality of the fingernails
[ more ] 		0001231
Abnormality of retinal pigmentation 0007703
Arachnodactyly
Long slender fingers
Spider fingers
[ more ] 		0001166
Bilateral single transverse palmar creases 0007598
Depressed nasal ridge
Flat nose
Recessed nasal ridge
[ more ] 		0000457
Generalized hirsutism
Excessive hairiness over body
0002230
Genu valgum
Knock knees
0002857
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ] 		0000316
Low anterior hairline
Low frontal hairline
Low-set frontal hairline
[ more ] 		0000294
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
White forelock
White part of hair above forehead
0002211
5%-29% of people have these symptoms
Hepatomegaly
Enlarged liver
0002240
Hypoplasia of the zygomatic bone
Cheekbone underdevelopment
Decreased size of cheekbone
Underdevelopment of cheekbone
[ more ] 		0010669
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes
[ more ] 		0000520
Recurrent cystitis
Recurrent bladder infections
0012786
Reduced bone mineral density
Low solidness and mass of the bones
0004349
Splenomegaly
Increased spleen size
0001744
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality
[ more ] 		0001939
Anemia
Low number of red blood cells or hemoglobin
0001903
Asthma 0002099
Autosomal recessive inheritance 0000007
Chronic lung disease 0006528
Convex nasal ridge
Beaked nose
Beaklike protrusion
Hooked nose
Polly beak nasal deformity
[ more ] 		0000444
Diffuse telangiectasia 0007489
Global developmental delay 0001263
Low posterior hairline
Low hairline at back of neck
0002162
Petechiae 0000967
Prolonged neonatal jaundice
Prolonged yellowing of skin in newborn
0006579
Prominent forehead
Pronounced forehead
Protruding forehead
[ more ] 		0011220
Ptosis
Drooping upper eyelid
0000508
Recurrent infections
Frequent infections
Frequent, severe infections
Increased frequency of infection
infections, recurrent
Predisposition to infections
Susceptibility to infection
[ more ] 		0002719
Recurrent pneumonia 0006532
Short nose
Decreased length of nose
Shortened nose
[ more ] 		0003196
Systemic lupus erythematosus 0002725
Thrombocytopenia
Low platelet count
0001873
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Last updated: 7/1/2020
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
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
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

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.
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
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.[1]

In most cases, people with prolidase deficiency experience a reduced quality of life because of infections and chronic pulmonary (lung) complications.[3] Life expectancy is often decreased, with infection being the most common cause of death.[1][3]
Last updated: 8/3/2017

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include Werner syndrome, beta-thalassemia, vasculitis (see these terms), autosomal dominant and recessive forms of hyper-IgE syndrome, sickle cell disease, pressure ulcers, and arterial and venous insufficiency.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Prolidase deficiency. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

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


  1. Ferreira C, Wang H. Prolidase Deficiency. GeneReviews. June 25, 2015; http://www.ncbi.nlm.nih.gov/books/NBK299584/.
  2. Prolidase deficiency. Genetics Home Reference (GHR). February 2012; https://ghr.nlm.nih.gov/condition/prolidase-deficiency.
  3. Jaeken J. Prolidase deficiency. Orphanet. July 2006; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=742.