Rare Oncology News

Disease Profile

Prolidase deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

E72.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Hyperimidodipeptiduria; Imidodipeptidase deficiency; Peptidase deficiency;

Categories

Blood Diseases; Congenital and Genetic Diseases; Metabolic disorders;

Summary

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]

Symptoms

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]

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.

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
Flat bridge of nose
Depressed bridge of nose
Low nasal root
Low nasal bridge
Flattened nasal bridge
Flat, nasal bridge
Flat nasal bridge

[ 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
Prominent eyes
Eyeballs bulging out
Protruding eyes
Prominent globes

[ 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
1%-4% of people have these symptoms
Anemia
Low number of red blood cells or hemoglobin
0001903
Asthma
0002099
Eczema
0000964
Elevated serum aspartate aminotransferase
0031956
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Febrile seizure (within the age range of 3 months to 6 years)
Fever induced seizures
0002373
Increased circulating antibody level
0010702
Mild global developmental delay
0011342
Petechiae
0000967
Prolonged neonatal jaundice
Prolonged yellowing of skin in newborn
0006579
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Systemic lupus erythematosus
0002725
Thrombocytopenia
Low platelet count
0001873
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Childhood onset
Symptoms begin in childhood
0011463
Chronic lung disease
0006528

Cause

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]

Diagnosis

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]

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.

    Treatment

    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.

    Organizations

    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

      Learn more

      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.

          References

          1. Ferreira C, Wang H. Prolidase Deficiency. GeneReviews. June 25, 2015; https://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; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=742.

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