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Prolidase deficiency

MedGen UID:
120647
Concept ID:
C0268532
Disease or Syndrome
Synonyms: Prolidase Deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Hyperimidodipeptiduria (410055005); Hyperimidodipeptiduria due to proline dipeptidase deficiency (410055005); Iminodipeptiduria (410055005); Deficiency of imidodipeptidase (360969006); Deficiency of prolidase (360994007); Deficiency of proline dipeptidase (361010007)
 
Gene: PEPD
Cytogenetic location: 19q13.11
OMIM: 170100

Definition

Prolidase deficiency is a rare autosomal recessive multisystem disorder associated with massive imidodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. The disorder is clinically heterogeneous and severity varies widely. Features include chronic, slowly healing ulcerations, mainly on the legs and feet. The ulcers are often preceded by other dermatologic manifestations that may occur anywhere and include erythematous papular eruptions, telangiectasias with pruritus and photosensitivity, impetigo-like eruptions, pruritic eczematous lesions, and necrotic papules. Mild to severe mental retardation is often a feature, and recurrent respiratory tract infections, sometimes fatal, are common. Facial dysmorphism may include low hairline and hirsutism, saddle nose, ocular hypertelorism, micrognathia, a high-arched palate, mandibular protrusion, and exophthalmos. Clinical manifestations are usually detectable after birth or in early childhood, but late-onset cases have been reported (summary by Lupi et al., 2008). [from OMIM]

Additional description

From GHR
Prolidase deficiency is a disorder that causes a wide variety of symptoms. The disorder typically becomes apparent during infancy. Affected individuals may have enlargement of the spleen (splenomegaly); in some cases, both the spleen and liver are enlarged (hepatosplenomegaly). Diarrhea, vomiting, and dehydration may also occur. People with prolidase deficiency are susceptible to severe infections of the skin or ears, or potentially life-threatening respiratory tract infections. Some individuals with prolidase deficiency have chronic lung disease. 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). Affected children may experience delayed development, and about 75 percent of people with prolidase deficiency have intellectual disability that may range from mild to severe. People with prolidase deficiency often develop skin lesions, especially on their hands, feet, lower legs, and face. The severity of the skin involvement, which usually begins during childhood, may range from a mild rash to severe skin ulcers. Skin ulcers, especially on the legs, may not heal completely, resulting in complications including infection and amputation. The severity of symptoms in prolidase deficiency varies greatly among affected individuals. Some people with this disorder do not have any symptoms. In these individuals the condition can be detected by laboratory tests such as newborn screening tests or tests offered to relatives of affected individuals.  http://ghr.nlm.nih.gov/condition/prolidase-deficiency

Clinical features

Urinary bladder inflammation
MedGen UID:
451892
Concept ID:
CN117470
Finding
`Inflammation`(MPATH:212) of the `urinary bladder` (FMA:15900).
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Convex nasal ridge
MedGen UID:
786052
Concept ID:
CN000415
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
Abnormal facial shape
MedGen UID:
505048
Concept ID:
CN001810
Finding
An abnormal morphology (form) of the face or its components.
Short nose
MedGen UID:
505478
Concept ID:
CN002885
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Depressed nasal bridge
MedGen UID:
446656
Concept ID:
CN004681
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Cheekbone underdevelopment
MedGen UID:
430039
Concept ID:
CN009495
Finding
Underdevelopment of the `zygomatic bone` (FMA:52747). That is, a reduction in size of the zygomatic process of the temporal bone of the skull, which forms the middle and lateral inferior orbital margin.
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Visual impairment
MedGen UID:
504469
Concept ID:
CN000473
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Hearing impairment
MedGen UID:
446352
Concept ID:
CN000341
Finding
A `decreased magnitude` (PATO:0002018) of the `sensory perception of sound` (GO:0007605).
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Genu valgum
MedGen UID:
505373
Concept ID:
CN002582
Finding
The legs angle inward, such that the knees are close together and the ankles far apart.
Abnormality of the hip bone
MedGen UID:
425136
Concept ID:
CN002954
Finding
An abnormality of the `hip bone` (FMA:16585).
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally `increased size` (PATO:0000586) of the `liver` (FMA:7197).
Prolonged neonatal jaundice
MedGen UID:
505938
Concept ID:
CN005732
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Finding
A disorder characterized by the presence of excessive hair growth in women in anatomic sites where growth is considered to be a secondary male characteristic (beard, moustache, chest, abdomen), where hair growth is under androgen control.
Petechiae
MedGen UID:
504665
Concept ID:
CN000905
Finding
Petechiae are pinpoint-sized reddish/purple spots, resembling a rash, that appear just under the skin or a mucous membrane when capillaries have ruptured and some superficial bleeding into the skin has happened. This term refers to an abnormally increased susceptibility to developing petechiae.
Pruritus
MedGen UID:
504677
Concept ID:
CN000926
Finding
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.
Cutaneous photosensitivity
MedGen UID:
428240
Concept ID:
CN000929
Finding
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Abnormality of the fingernails
MedGen UID:
446395
Concept ID:
CN001134
Finding
An abnormality of the `fingernails` (FMA:54327).
White forelock
MedGen UID:
505158
Concept ID:
CN002004
Finding
A triangular depigmented region of white hairs located in the anterior midline of the scalp.
Prolonged neonatal jaundice
MedGen UID:
505938
Concept ID:
CN005732
Finding
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
Diffuse telangiectasia
MedGen UID:
506080
Concept ID:
CN006566
Finding
Telangiectases (small dilated blood vessels) with a diffuse localization.
Skin ulcer
MedGen UID:
506561
Concept ID:
CN117783
Finding
A discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis and even subcutaneous fat.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.
Anemia
MedGen UID:
56401
Concept ID:
C0162119
Finding
A laboratory test result which indicates decreased levels of hemoglobin in a biological specimen.
Petechiae
MedGen UID:
504665
Concept ID:
CN000905
Finding
Petechiae are pinpoint-sized reddish/purple spots, resembling a rash, that appear just under the skin or a mucous membrane when capillaries have ruptured and some superficial bleeding into the skin has happened. This term refers to an abnormally increased susceptibility to developing petechiae.
Asthma
MedGen UID:
505101
Concept ID:
CN001900
Finding
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Chronic lung disease
MedGen UID:
505923
Concept ID:
CN005686
Finding
According to the definitions of the American and British Thoracic Societies, including pulmonary functional tests, X-rays, and CT scans for items such as fibrosis, bronchiectasis, bullae, emphysema, nodular or lymphomatous abnormalities.
Recurrent pneumonia
MedGen UID:
505924
Concept ID:
CN005690
Finding
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Asthma
MedGen UID:
505101
Concept ID:
CN001900
Finding
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Systemic lupus erythematosus
MedGen UID:
505336
Concept ID:
CN002475
Finding
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes.
Recurrent pneumonia
MedGen UID:
505924
Concept ID:
CN005690
Finding
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGProlidase deficiency

Recent clinical studies

Etiology

Pandit RA, Chen CJ, Butt TA, Islam N
Gene 2013 Mar 10;516(2):316-9. Epub 2012 Dec 31 doi: 10.1016/j.gene.2012.12.070. [Epub ahead of print] PMID: 23287645
Falik-Zaccai TC, Khayat M, Luder A, Frenkel P, Magen D, Brik R, Gershoni-Baruch R, Mandel H
Am J Med Genet B Neuropsychiatr Genet 2010 Jan 5;153B(1):46-56. doi: 10.1002/ajmg.b.30945. PMID: 19308961
Wang H, Kurien BT, Lundgren D, Patel NC, Kaufman KM, Miller DL, Porter AC, D'Souza A, Nye L, Tumbush J, Hupertz V, Kerr DS, Kurono S, Matsumoto H, Scofield RH
Am J Med Genet A 2006 Mar 15;140(6):580-5. doi: 10.1002/ajmg.a.31134. PMID: 16470701
Shrinath M, Walter JH, Haeney M, Couriel JM, Lewis MA, Herrick AL
Arch Dis Child 1997 May;76(5):441-4. PMID: 9196362Free PMC Article
Powell GF, Kurosky A, Maniscalco RM
J Pediatr 1977 Aug;91(2):242-6. PMID: 874681

Diagnosis

Dunn R, Varigos G, Winship I
Clin Dysmorphol 2011 Oct;20(4):194-9. doi: 10.1097/MCD.0b013e3283486cbd. PMID: 21760498
Besio R, Monzani E, Gioia R, Nicolis S, Rossi A, Casella L, Forlino A
Clin Chim Acta 2011 Sep 18;412(19-20):1814-20. Epub 2011 Jun 15 doi: 10.1016/j.cca.2011.06.011. [Epub ahead of print] PMID: 21699887
Klar A, Navon-Elkan P, Rubinow A, Branski D, Hurvitz H, Christensen E, Khayat M, Falik-Zaccai TC
Eur J Pediatr 2010 Jun;169(6):727-32. Epub 2009 Nov 24 doi: 10.1007/s00431-009-1102-1. [Epub ahead of print] PMID: 19937054
Di Rocco M, Fantasia AR, Taro M, Loy A, Forlino A, Martini A
J Inherit Metab Dis 2007 Oct;30(5):814. Epub 2007 Jun 14 doi: 10.1007/s10545-007-0496-z. [Epub ahead of print] PMID: 17570078
Shrinath M, Walter JH, Haeney M, Couriel JM, Lewis MA, Herrick AL
Arch Dis Child 1997 May;76(5):441-4. PMID: 9196362Free PMC Article

Therapy

Dunn R, Dolianitis C
Australas J Dermatol 2008 Nov;49(4):237-8. doi: 10.1111/j.1440-0960.2008.00485.x. PMID: 18855790
Lupi A, Tenni R, Rossi A, Cetta G, Forlino A
Amino Acids 2008 Nov;35(4):739-52. Epub 2008 Mar 14 doi: 10.1007/s00726-008-0055-4. [Epub ahead of print] PMID: 18340504
Zhang J, Sugahara K, Yasuda K, Kodama H, Sagara Y, Kodama H
Free Radic Biol Med 1998 Mar 15;24(5):689-98. PMID: 9586797
Jemec GB, Moe AT
Pediatr Dermatol 1996 Jan-Feb;13(1):58-60. PMID: 8919529
Powell GF, Maniscalco RM
Metabolism 1976 May;25(5):503-8. PMID: 772363

Prognosis

Besio R, Gioia R, Cossu F, Monzani E, Nicolis S, Cucca L, Profumo A, Casella L, Tenni R, Bolognesi M, Rossi A, Forlino A
PLoS One 2013;8(3):e58792. Epub 2013 Mar 13 doi: 10.1371/journal.pone.0058792. PMID: 23516557Free PMC Article
Klar A, Navon-Elkan P, Rubinow A, Branski D, Hurvitz H, Christensen E, Khayat M, Falik-Zaccai TC
Eur J Pediatr 2010 Jun;169(6):727-32. Epub 2009 Nov 24 doi: 10.1007/s00431-009-1102-1. [Epub ahead of print] PMID: 19937054
Lupi A, Casado B, Soli M, Bertazzoni M, Annovazzi L, Viglio S, Cetta G, Iadarola P
Br J Dermatol 2002 Dec;147(6):1237-40. PMID: 12452876
Mandel H, Abeling N, Gutman A, Berant M, Scholten EG, Sheiman C, Luder A, van Gennip AH
Prenat Diagn 2000 Nov;20(11):927-9. PMID: 11113899
Shrinath M, Walter JH, Haeney M, Couriel JM, Lewis MA, Herrick AL
Arch Dis Child 1997 May;76(5):441-4. PMID: 9196362Free PMC Article

Clinical prediction guides

Besio R, Gioia R, Cossu F, Monzani E, Nicolis S, Cucca L, Profumo A, Casella L, Tenni R, Bolognesi M, Rossi A, Forlino A
PLoS One 2013;8(3):e58792. Epub 2013 Mar 13 doi: 10.1371/journal.pone.0058792. PMID: 23516557Free PMC Article
Mandel H, Abeling N, Gutman A, Berant M, Scholten EG, Sheiman C, Luder A, van Gennip AH
Prenat Diagn 2000 Nov;20(11):927-9. PMID: 11113899
Dolenga M, Hechtman P
Pediatr Res 1992 Oct;32(4):479-82. doi: 10.1203/00006450-199210000-00020. PMID: 1437403
Kodama H, Nakamura H, Sugahara K, Numajiri Y
J Chromatogr 1990 May 18;527(2):279-88. PMID: 2387877
Endo F, Matsuda I, Ogata A, Tanaka S
Pediatr Res 1982 Mar;16(3):227-31. PMID: 7063276

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