MCID: PRL019
MIFTS: 41

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 53 72 23 49 24 55 71 36 28 13 41
Hyperimidodipeptiduria 49 24 55
Pd 49 24 71
Imidodipeptidase Deficiency 49 24
Peptidase Deficiency 49 24
Deficiency of Prolidase 69

Characteristics:

Orphanet epidemiological data:

55
prolidase deficiency
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Canada); Age of onset: Adult,Childhood,Infancy,Neonatal; Age of death: any age;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
median age at diagnosis 7 years
highly variable expression


HPO:

31
prolidase deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Prolidase Deficiency

OMIM : 53 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 glaucoma-related pigment dispersion syndrome, and has symptoms including pruritus, dry skin and hypertelorism. An important gene associated with Prolidase Deficiency is PEPD (Peptidase D). Affiliated tissues include skin, liver and spleen.

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.

NIH Rare Diseases : 49 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

Genetics Home Reference : 24 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.

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

GeneReviews: NBK299584

Related Diseases for Prolidase Deficiency

Diseases related to Prolidase Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 51)
# Related Disease Score Top Affiliating Genes
1 parkinson disease, late-onset 12.1
2 glaucoma-related pigment dispersion syndrome 11.6
3 pendred syndrome 11.5
4 multiple system atrophy 1 11.1
5 personality disorder 11.1
6 corticobasal degeneration 11.1
7 ehlers-danlos syndrome, spondylodysplastic type, 1 11.0
8 spondylodysplastic ehlers-danlos syndrome 11.0
9 parkinson disease 19a, juvenile-onset 10.9
10 pendred syndrome/nonsyndromic enlarged vestibular aqueduct 10.9
11 dementia, lewy body 10.8
12 pick disease of brain 10.8
13 epilepsy, pyridoxine-dependent 10.8
14 thyroxine-binding globulin quantitative trait locus 10.8
15 convulsions, familial infantile, with paroxysmal choreoathetosis 10.8
16 kufor-rakeb syndrome 10.8
17 frontotemporal lobar degeneration with tdp43 inclusions, grn-related 10.8
18 parkinson disease 17 10.8
19 parkinson disease 18, autosomal dominant 10.8
20 parkinson disease 20, early-onset 10.8
21 parkinson disease 21 10.8
22 diphallia 10.8
23 pancreas disease 10.1
24 endotheliitis 10.1
25 peritonitis 10.1
26 branchiootic syndrome 1 10.0
27 systemic lupus erythematosus 10.0
28 lupus erythematosus 10.0
29 deafness, autosomal recessive 4, with enlarged vestibular aqueduct 10.0
30 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.0
31 cervicitis 10.0
32 neuronitis 9.9
33 rem sleep behavior disorder 9.9
34 tremor 9.9
35 blood group, i system 9.9
36 panic disorder 9.9
37 thyroiditis 9.9
38 fibrosis of extraocular muscles, congenital, 1 9.7
39 cystic fibrosis 9.7
40 hydrops, lactic acidosis, and sideroblastic anemia 9.7
41 arthritis 9.7
42 hematopoietic stem cell transplantation 9.7
43 inflammatory bowel disease 9.7
44 microcytic anemia 9.7
45 myopia 9.7
46 squamous cell carcinoma 9.7
47 cutaneous solitary mastocytoma 9.7
48 lung disease 9.7
49 vasculitis 9.7
50 hyper ige syndrome 9.7

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:

53
Head And Neck Eyes:
hypertelorism
ptosis
exophthalmos
ocular proptosis
upslanting or downslanting palpebral fissures

Abdomen Liver:
hepatomegaly
jaundice, neonatal

Hematology:
anemia
thrombocytopenia
petechiae

Respiratory Lung:
asthma
chronic lung disease
pulmonary infections, recurrent

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

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

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

Abdomen Spleen:
splenomegaly

Head And Neck Face:
prominent forehead
facial dysmorphism

Skin Nails Hair Hair:
low posterior hairline

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

Neurologic Central Nervous System:
developmental delay

Head And Neck Mouth:
slender upper lip


Clinical features from OMIM:

170100

Human phenotypes related to Prolidase Deficiency:

55 31 (show top 50) (show all 56)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pruritus 55 31 hallmark (90%) Very frequent (99-80%) HP:0000989
2 dry skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0000958
3 hypertelorism 55 31 frequent (33%) Frequent (79-30%) HP:0000316
4 genu valgum 55 31 frequent (33%) Frequent (79-30%) HP:0002857
5 intellectual disability 55 31 occasional (7.5%) Occasional (29-5%) HP:0001249
6 hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000365
7 splenomegaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0001744
8 recurrent respiratory infections 55 31 hallmark (90%) Very frequent (99-80%) HP:0002205
9 hepatomegaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0002240
10 depressed nasal bridge 55 31 hallmark (90%) Very frequent (99-80%) HP:0005280
11 carious teeth 55 31 hallmark (90%) Very frequent (99-80%) HP:0000670
12 abnormal facial shape 55 31 hallmark (90%) Very frequent (99-80%) HP:0001999
13 visual impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000505
14 abnormality of retinal pigmentation 55 31 frequent (33%) Frequent (79-30%) HP:0007703
15 micrognathia 55 31 frequent (33%) Frequent (79-30%) HP:0000347
16 palmoplantar keratoderma 55 31 hallmark (90%) Very frequent (99-80%) HP:0000982
17 thin skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0000963
18 generalized hirsutism 55 31 frequent (33%) Frequent (79-30%) HP:0002230
19 abnormality of the hip bone 55 31 hallmark (90%) Very frequent (99-80%) HP:0003272
20 reduced bone mineral density 55 31 occasional (7.5%) Occasional (29-5%) HP:0004349
21 abnormality of the fingernails 55 31 frequent (33%) Frequent (79-30%) HP:0001231
22 skin ulcer 55 31 hallmark (90%) Very frequent (99-80%) HP:0200042
23 depressed nasal ridge 55 31 frequent (33%) Frequent (79-30%) HP:0000457
24 arachnodactyly 55 31 frequent (33%) Frequent (79-30%) HP:0001166
25 bilateral single transverse palmar creases 55 31 frequent (33%) Frequent (79-30%) HP:0007598
26 erythema 55 31 hallmark (90%) Very frequent (99-80%) HP:0010783
27 low anterior hairline 55 31 frequent (33%) Frequent (79-30%) HP:0000294
28 proptosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000520
29 cutaneous photosensitivity 55 31 hallmark (90%) Very frequent (99-80%) HP:0000992
30 papule 55 31 hallmark (90%) Very frequent (99-80%) HP:0200034
31 white forelock 55 31 frequent (33%) Frequent (79-30%) HP:0002211
32 abnormality of the middle ear 55 31 hallmark (90%) Very frequent (99-80%) HP:0000370
33 crusting erythematous dermatitis 55 31 hallmark (90%) Very frequent (99-80%) HP:0007473
34 recurrent cystitis 55 31 occasional (7.5%) Occasional (29-5%) HP:0012786
35 ptosis 31 HP:0000508
36 global developmental delay 31 HP:0001263
37 short nose 31 HP:0003196
38 prominent forehead 31 HP:0011220
39 abnormality of metabolism/homeostasis 31 HP:0001939
40 anemia 31 HP:0001903
41 hyperkeratosis 55 Very frequent (99-80%)
42 low posterior hairline 31 HP:0002162
43 thrombocytopenia 31 HP:0001873
44 abnormality of the immune system 55 Very frequent (99-80%)
45 aplasia/hypoplasia of the skin 55 Very frequent (99-80%)
46 asthma 31 HP:0002099
47 recurrent pneumonia 31 HP:0006532
48 petechiae 31 HP:0000967
49 cheekbone underdevelopment 55 Occasional (29-5%)
50 convex nasal ridge 31 HP:0000444

UMLS symptoms related to Prolidase Deficiency:


petechiae of skin

Drugs & Therapeutics for Prolidase Deficiency

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Prolidase Enzyme Activity in Stroke Patients Completed NCT03334968

Search NIH Clinical Center for Prolidase Deficiency

Cochrane evidence based reviews: prolidase deficiency

Genetic Tests for Prolidase Deficiency

Genetic tests related to Prolidase Deficiency:

# Genetic test Affiliating Genes
1 Prolidase Deficiency 28 PEPD

Anatomical Context for Prolidase Deficiency

MalaCards organs/tissues related to Prolidase Deficiency:

38
Skin, Liver, Spleen, Lung, Bone, Neutrophil

Publications for Prolidase Deficiency

Articles related to Prolidase Deficiency:

(show top 50) (show all 127)
# 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
Prolidase deficiency in two sisters with recurrent ulcerations of the lower extremities. ( 29058805 )
2017
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
A Rare Cause of Lower Extremity Ulcers: Prolidase Deficiency. ( 26637345 )
2016
7
Pulmonary manifestations of prolidase deficiency. ( 27132891 )
2016
8
INFLAMMATORY BOWEL DISEASE-LIKE PHENOTYPE IN A YOUNG GIRL WITH PROLIDASE DEFICIENCY: A NEW SPECTRUM OF CLINICAL MANIFESTATION. ( 26349190 )
2015
9
A case of prolidase deficiency accompanying leg ulcers. ( 25691319 )
2015
10
Solitary Mastocytoma of the Eyelid in an Adult Patient With Prolidase Deficiency. ( 25603535 )
2015
11
Prolidase deficiency: dento-facial aspects in a paediatric patient. ( 25101509 )
2014
12
Prolidase deficiency: dento-facial aspects in a paediatric patient. ( 25299025 )
2014
13
Prolidase deficiency breaks tolerance to lupus-associated antigens. ( 24330273 )
2013
14
Massive Splenomegaly Secondary to Prolidase Deficiency. ( 23811574 )
2013
15
Prolidase deficiency associated with systemic lupus erythematosus (SLE): single site experience and literature review. ( 22726576 )
2012
16
Partial Rescue of Biochemical Parameters After Hematopoietic Stem Cell Transplantation in a Patient with Prolidase Deficiency Due to Two Novel PEPD Mutations. ( 23430876 )
2012
17
A photographic essay of prolidase deficiency. ( 21760498 )
2011
18
Developmental cardiac hypertrophy in a mouse model of prolidase deficiency. ( 21472842 )
2011
19
Improved prolidase activity assay allowed enzyme kinetic characterization and faster prolidase deficiency diagnosis. ( 21699887 )
2011
20
A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability. ( 19308961 )
2010
21
Prolidase deficiency: it looks like systemic lupus erythematosus but it is not. ( 19937054 )
2010
22
Prolidase deficiency: a rare aetiology of arthritis. ( 20031465 )
2010
23
Characterization of prolidase I and II purified from normal human erythrocytes: comparison with prolidase in erythrocytes from a patient with prolidase deficiency. ( 19263194 )
2009
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
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
27
Different effects of sulfur amino acids on prolidase and prolinase activity in normal and prolidase-deficient human erythrocytes. ( 16899234 )
2007
28
Chronic lung disease and cystic fibrosis phenotype in prolidase deficiency: a newly recognized association. ( 17517257 )
2007
29
Systemic lupus erythematosus-like disease in a 6-year-old boy with prolidase deficiency. ( 17570078 )
2007
30
Prolidase deficiency and the biochemical assays used in its diagnosis. ( 16298326 )
2006
31
Ulcus cruris associated with prolidase deficiency. ( 17459310 )
2006
32
Prolidase deficiency associated with hemoglobin O trait and microcytic anemia. ( 16863530 )
2006
33
A nonsense mutation of PEPD in four Amish children with prolidase deficiency. ( 16470701 )
2006
34
[Effective therapy with a glycine-proline ointment in a patient with recurrent ulcers from prolidase deficiency]. ( 17166065 )
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
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
37
A homozygous missense mutation in PEPD encoding peptidase D causes prolidase deficiency associated with hyper-IgE syndrome. ( 16681595 )
2006
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
Intracellular delivery of liposome-encapsulated prolidase in cultured fibroblasts from prolidase-deficient patients. ( 15653144 )
2005
40
Characteristics of prolinase against various iminodipeptides in erythrocyte lysates from a normal human and a patient with prolidase deficiency. ( 15552267 )
2004
41
Prolidase deficiency: case reports of two Argentinian brothers. ( 15357754 )
2004
42
Leg ulcers secondary to prolidase deficiency. ( 15632738 )
2004
43
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
44
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
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
Characteristics of prolidase from the erythrocytes of normal humans and patients with prolidase deficiency and their mother. ( 14580160 )
2003
47
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
48
Prolidase deficiency. ( 11895514 )
2002
49
Therapeutic apheresis exchange in two patients with prolidase deficiency. ( 12452876 )
2002
50
Prolidase deficiency with hyperimmunoglobulin E: a case report. ( 12000488 )
2002

Variations for Prolidase Deficiency

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

71
# 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)
# 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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....