MCID: PRL019
MIFTS: 40

Prolidase Deficiency

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Skin diseases, Metabolic diseases

Aliases & Classifications for Prolidase Deficiency

MalaCards integrated aliases for Prolidase Deficiency:

Name: Prolidase Deficiency 54 23 50 24 25 56 71 29 13 42
Hyperimidodipeptiduria 50 25 56
Pd 50 25 71
Imidodipeptidase Deficiency 50 25
Peptidase Deficiency 50 25
Deficiency of Prolidase 69

Characteristics:

Orphanet epidemiological data:

56
prolidase deficiency
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Canada); Age of onset: Adult,Childhood,Infancy,Neonatal; Age of death: any age;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
median age at diagnosis 7 years
highly variable expression


HPO:

32
prolidase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Prolidase Deficiency

OMIM : 54
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). (170100)

MalaCards based summary : Prolidase Deficiency, also known as hyperimidodipeptiduria, is related to parkinson disease, late-onset and pendred syndrome, and has symptoms including visual impairment, recurrent respiratory infections and palmoplantar keratoderma. An important gene associated with Prolidase Deficiency is PEPD (Peptidase D). Affiliated tissues include skin, liver and spleen.

Genetics Home Reference : 25 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.

NIH Rare Diseases : 50 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: 3/25/2016

UniProtKB/Swiss-Prot : 71 Prolidase deficiency: A multisystem disorder associated with massive iminodipeptiduria and lack of or reduced prolidase activity in erythrocytes, leukocytes, or cultured fibroblasts. Clinical features include skin ulcers, developmental delay, recurrent infections, and a characteristic facies.

Wikipedia : 72 Prolidase deficiency (PD) is an extremely uncommon autosomal recessive disorder associated with collagen... more...

GeneReviews: NBK299584

Related Diseases for Prolidase Deficiency

Graphical network of the top 20 diseases related to Prolidase Deficiency:



Diseases related to Prolidase Deficiency

Symptoms & Phenotypes for Prolidase Deficiency

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
developmental delay

Abdomen- Spleen:
splenomegaly

Hematology:
thrombocytopenia
anemia
petechiae

Head And Neck- Nose:
small nose
beaked nose
low nasal root

Skin Nails & Hair- Hair:
low posterior hairline

Skin Nails & Hair- Skin:
diffuse telangiectases
crusting erythematous dermatitis
impetigo-like eruptions
pruritic eczematous lesions
severe progressive ulceration of lower extremities

Abdomen- Liver:
hepatomegaly
jaundice, neonatal

Head And Neck- Eyes:
ptosis
hypertelorism
exophthalmos
ocular proptosis
upward or downward slanting palpebral fissures

Head And Neck- Face:
prominent forehead
facial dysmorphism

Immunology:
systemic lupus erythematosus
elevated immunoglobulins, particularly ige
increased frequency of infection

Head And Neck- Mouth:
slender upper lip

Laboratory- Abnormalities:
hyperimidodipeptiduria
deficiency of prolidase activity in erythrocytes, leukocytes, or fibroblasts


Clinical features from OMIM:

170100

Human phenotypes related to Prolidase Deficiency:

56 32 (show top 50) (show all 56)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 visual impairment 56 32 frequent (33%) Frequent (79-30%) HP:0000505
2 recurrent respiratory infections 56 32 hallmark (90%) Very frequent (99-80%) HP:0002205
3 palmoplantar keratoderma 56 32 hallmark (90%) Very frequent (99-80%) HP:0000982
4 hepatomegaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0002240
5 splenomegaly 56 32 occasional (7.5%) Occasional (29-5%) HP:0001744
6 micrognathia 56 32 frequent (33%) Frequent (79-30%) HP:0000347
7 depressed nasal bridge 56 32 hallmark (90%) Very frequent (99-80%) HP:0005280
8 hypertelorism 56 32 frequent (33%) Frequent (79-30%) HP:0000316
9 proptosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0000520
10 genu valgum 56 32 frequent (33%) Frequent (79-30%) HP:0002857
11 thin skin 56 32 hallmark (90%) Very frequent (99-80%) HP:0000963
12 low anterior hairline 56 32 frequent (33%) Frequent (79-30%) HP:0000294
13 intellectual disability 56 32 occasional (7.5%) Occasional (29-5%) HP:0001249
14 white forelock 56 32 frequent (33%) Frequent (79-30%) HP:0002211
15 dry skin 56 32 hallmark (90%) Very frequent (99-80%) HP:0000958
16 arachnodactyly 56 32 frequent (33%) Frequent (79-30%) HP:0001166
17 pruritus 56 32 hallmark (90%) Very frequent (99-80%) HP:0000989
18 erythema 56 32 hallmark (90%) Very frequent (99-80%) HP:0010783
19 hearing impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000365
20 carious teeth 56 32 hallmark (90%) Very frequent (99-80%) HP:0000670
21 generalized hirsutism 56 32 frequent (33%) Frequent (79-30%) HP:0002230
22 depressed nasal ridge 56 32 frequent (33%) Frequent (79-30%) HP:0000457
23 crusting erythematous dermatitis 56 32 hallmark (90%) Very frequent (99-80%) HP:0007473
24 cutaneous photosensitivity 56 32 hallmark (90%) Very frequent (99-80%) HP:0000992
25 bilateral single transverse palmar creases 56 32 frequent (33%) Frequent (79-30%) HP:0007598
26 abnormal facial shape 56 32 hallmark (90%) Very frequent (99-80%) HP:0001999
27 abnormality of retinal pigmentation 56 32 frequent (33%) Frequent (79-30%) HP:0007703
28 abnormality of the hip bone 56 32 hallmark (90%) Very frequent (99-80%) HP:0003272
29 reduced bone mineral density 56 32 occasional (7.5%) Occasional (29-5%) HP:0004349
30 abnormality of the fingernails 56 32 frequent (33%) Frequent (79-30%) HP:0001231
31 skin ulcer 56 32 hallmark (90%) Very frequent (99-80%) HP:0200042
32 papule 56 32 hallmark (90%) Very frequent (99-80%) HP:0200034
33 abnormality of the middle ear 56 32 hallmark (90%) Very frequent (99-80%) HP:0000370
34 recurrent cystitis 56 32 occasional (7.5%) Occasional (29-5%) HP:0012786
35 hirsutism 56 Frequent (79-30%)
36 ptosis 32 HP:0000508
37 thrombocytopenia 32 HP:0001873
38 anemia 32 HP:0001903
39 prominent forehead 32 HP:0011220
40 short nose 32 HP:0003196
41 global developmental delay 32 HP:0001263
42 hyperkeratosis 56 Very frequent (99-80%)
43 systemic lupus erythematosus 32 HP:0002725
44 petechiae 32 HP:0000967
45 low posterior hairline 32 HP:0002162
46 asthma 32 HP:0002099
47 recurrent pneumonia 32 HP:0006532
48 chronic lung disease 32 HP:0006528
49 prolonged neonatal jaundice 32 HP:0006579
50 convex nasal ridge 32 HP:0000444

Drugs & Therapeutics for Prolidase Deficiency

Search Clinical Trials , NIH Clinical Center for Prolidase Deficiency

Cochrane evidence based reviews: prolidase deficiency

Genetic Tests for Prolidase Deficiency

Genetic tests related to Prolidase Deficiency:

id Genetic test Affiliating Genes
1 Prolidase Deficiency 29 24 PEPD

Anatomical Context for Prolidase Deficiency

MalaCards organs/tissues related to Prolidase Deficiency:

39
Skin, Liver, Spleen, Lung, Bone, Neutrophil

Publications for Prolidase Deficiency

Articles related to Prolidase Deficiency:

(show top 50) (show all 126)
id Title Authors Year
1
A Case Of 13-Year-Old Girl With Prolidase Deficiency. ( 28718266 )
2017
2
Hyperbaric oxygen therapy in the management of severe leg ulcers from prolidase deficiency. ( 28062424 )
2017
3
A Rare Cause of Lower Extremity Ulcers: Prolidase Deficiency. ( 26637345 )
2016
4
Spurious Elevation of Multiple Urine Amino Acids by Ion-Exchange Chromatography in Patients with Prolidase Deficiency. ( 27067078 )
2016
5
Prolidase Deficiency in a Mexican-American Patient Identified by Array CGH Reveals a Novel and the Largest PEPD Gene Deletion. ( 27385964 )
2016
6
Pulmonary manifestations of prolidase deficiency. ( 27132891 )
2016
7
A case of prolidase deficiency accompanying leg ulcers. ( 25691319 )
2015
8
Solitary Mastocytoma of the Eyelid in an Adult Patient With Prolidase Deficiency. ( 25603535 )
2015
9
INFLAMMATORY BOWEL DISEASE-LIKE PHENOTYPE IN A YOUNG GIRL WITH PROLIDASE DEFICIENCY: A NEW SPECTRUM OF CLINICAL MANIFESTATION. ( 26349190 )
2015
10
Prolidase deficiency: dento-facial aspects in a paediatric patient. ( 25101509 )
2014
11
Prolidase deficiency: dento-facial aspects in a paediatric patient. ( 25299025 )
2014
12
Massive Splenomegaly Secondary to Prolidase Deficiency. ( 23811574 )
2013
13
Prolidase deficiency breaks tolerance to lupus-associated antigens. ( 24330273 )
2013
14
Partial Rescue of Biochemical Parameters After Hematopoietic Stem Cell Transplantation in a Patient with Prolidase Deficiency Due to Two Novel PEPD Mutations. ( 23430876 )
2012
15
Prolidase deficiency associated with systemic lupus erythematosus (SLE): single site experience and literature review. ( 22726576 )
2012
16
A photographic essay of prolidase deficiency. ( 21760498 )
2011
17
Developmental cardiac hypertrophy in a mouse model of prolidase deficiency. ( 21472842 )
2011
18
Improved prolidase activity assay allowed enzyme kinetic characterization and faster prolidase deficiency diagnosis. ( 21699887 )
2011
19
Prolidase deficiency: a rare aetiology of arthritis. ( 20031465 )
2010
20
Prolidase deficiency: it looks like systemic lupus erythematosus but it is not. ( 19937054 )
2010
21
A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability. ( 19308961 )
2010
22
Characterization of prolidase I and II purified from normal human erythrocytes: comparison with prolidase in erythrocytes from a patient with prolidase deficiency. ( 19263194 )
2009
23
Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations. ( 18340504 )
2008
24
Prolidase deficiency: the use of topical proline for treatment of leg ulcers. ( 18855790 )
2008
25
Nasal reconstruction in a patient with prolidase deficiency syndrome. ( 18639509 )
2008
26
Different effects of sulfur amino acids on prolidase and prolinase activity in normal and prolidase-deficient human erythrocytes. ( 16899234 )
2007
27
Systemic lupus erythematosus-like disease in a 6-year-old boy with prolidase deficiency. ( 17570078 )
2007
28
Chronic lung disease and cystic fibrosis phenotype in prolidase deficiency: a newly recognized association. ( 17517257 )
2007
29
A nonsense mutation of PEPD in four Amish children with prolidase deficiency. ( 16470701 )
2006
30
Ulcus cruris associated with prolidase deficiency. ( 17459310 )
2006
31
A homozygous missense mutation in PEPD encoding peptidase D causes prolidase deficiency associated with hyper-IgE syndrome. ( 16681595 )
2006
32
[Effective therapy with a glycine-proline ointment in a patient with recurrent ulcers from prolidase deficiency]. ( 17166065 )
2006
33
Molecular characterisation of six patients with prolidase deficiency: identification of the first small duplication in the prolidase gene and of a mutation generating symptomatic and asymptomatic outcomes within the same family. ( 17142620 )
2006
34
Prolidase deficiency and the biochemical assays used in its diagnosis. ( 16298326 )
2006
35
The role of emerging techniques in the investigation of prolidase deficiency: from diagnosis to the development of a possible therapeutical approach. ( 16434239 )
2006
36
Prolidase deficiency associated with hemoglobin O trait and microcytic anemia. ( 16863530 )
2006
37
Intracellular delivery of liposome-encapsulated prolidase in cultured fibroblasts from prolidase-deficient patients. ( 15653144 )
2005
38
Characterization of prolidase activity in erythrocytes from a patient with prolidase deficiency: comparison with prolidase I and II purified from normal human erythrocytes. ( 16009141 )
2005
39
Characterization of a new PEPD allele causing prolidase deficiency in two unrelated patients: natural-occurrent mutations as a tool to investigate structure-function relationship. ( 15309682 )
2004
40
Effects of amino acids and its metabolites on prolidase activity against various iminodipeptides in erythrocytes from normal human and a patient with prolidase deficiency. ( 15530480 )
2004
41
Leg ulcers secondary to prolidase deficiency. ( 15632738 )
2004
42
Characteristics of prolinase against various iminodipeptides in erythrocyte lysates from a normal human and a patient with prolidase deficiency. ( 15552267 )
2004
43
Prolidase deficiency: case reports of two Argentinian brothers. ( 15357754 )
2004
44
Characteristics of prolidase from the erythrocytes of normal humans and patients with prolidase deficiency and their mother. ( 14580160 )
2003
45
Optimization of a capillary electrophoretic method to detect and quantify the Gly-Pro dipeptide in complex matrices from long term cultured prolidase deficiency fibroblasts. ( 12957177 )
2003
46
Mutation analysis of five new patients affected by prolidase deficiency: the lack of enzyme activity causes necrosis-like cell death in cultured fibroblasts. ( 12384772 )
2002
47
Prolidase deficiency with hyperimmunoglobulin E: a case report. ( 12000488 )
2002
48
Therapeutic apheresis exchange in two patients with prolidase deficiency. ( 12452876 )
2002
49
Prolidase deficiency. ( 11895514 )
2002
50
Prolidase deficiency diagnosed by 1H NMR spectroscopy of urine. ( 11916317 )
2001

Variations for Prolidase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Prolidase Deficiency:

71
id Symbol AA change Variation ID SNP ID
1 PEPD p.Asp276Asn VAR_004404 rs121917721
2 PEPD p.Gly448Arg VAR_004405 rs121917724
3 PEPD p.Arg184Gln VAR_011614 rs121917722
4 PEPD p.Gly278Asp VAR_011615 rs121917723

ClinVar genetic disease variations for Prolidase Deficiency:

6 (show all 12)
id Gene Variation Type Significance SNP ID Assembly Location
1 PEPD NM_000285.3(PEPD): c.826G> A (p.Asp276Asn) single nucleotide variant Pathogenic rs121917721 GRCh37 Chromosome 19, 33892768: 33892768
2 PEPD NM_000285.3(PEPD): c.1153_1344del192 (p.Gly385_Gly448del) deletion Pathogenic GRCh38 Chromosome 19, 33387843: 33388624
3 PEPD NM_000285.3(PEPD): c.551G> A (p.Arg184Gln) single nucleotide variant Pathogenic rs121917722 GRCh37 Chromosome 19, 33954966: 33954966
4 PEPD NM_000285.3(PEPD): c.833G> A (p.Gly278Asp) single nucleotide variant Pathogenic rs121917723 GRCh37 Chromosome 19, 33892761: 33892761
5 PEPD NM_000285.3(PEPD): c.1342G> A (p.Gly448Arg) single nucleotide variant Pathogenic rs121917724 GRCh37 Chromosome 19, 33878798: 33878798
6 PEPD NM_000285.3(PEPD): c.1359_1361delGGA (p.Glu453del) deletion Pathogenic rs757386104 GRCh38 Chromosome 19, 33387465: 33387467
7 PEPD NM_000285.3(PEPD): c.793C> T (p.Arg265Ter) single nucleotide variant Pathogenic rs121917725 GRCh37 Chromosome 19, 33902603: 33902603
8 PEPD NM_000285.3(PEPD): c.1234G> A (p.Glu412Lys) single nucleotide variant Pathogenic rs267606944 GRCh37 Chromosome 19, 33878906: 33878906
9 PEPD NM_000285.3(PEPD): c.611_623dupAGGCCCACCGTGA (p.Val209Glyfs) duplication Pathogenic rs794728008 GRCh38 Chromosome 19, 33463988: 33464000
10 PEPD NM_000285.3(PEPD): c.605C> T (p.Ser202Phe) single nucleotide variant Pathogenic rs267606943 GRCh37 Chromosome 19, 33954912: 33954912
11 PEPD NM_000285.3(PEPD): c.1103T> G (p.Leu368Arg) single nucleotide variant Pathogenic rs797045185 GRCh38 Chromosome 19, 33391344: 33391344
12 PEPD NM_000285.3(PEPD): c.634G> C (p.Ala212Pro) single nucleotide variant Pathogenic rs747700126 GRCh38 Chromosome 19, 33463032: 33463032

Expression for Prolidase Deficiency

Search GEO for disease gene expression data for Prolidase Deficiency.

Pathways for Prolidase Deficiency

GO Terms for Prolidase Deficiency

Sources for Prolidase Deficiency

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7 CNVD
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67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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