WRS
MCID: WLC001
MIFTS: 40

Wolcott-Rallison Syndrome (WRS) malady

Categories: Genetic diseases, Rare diseases, Bone diseases, Endocrine diseases, Fetal diseases

Aliases & Classifications for Wolcott-Rallison Syndrome

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Sources:
12diseasecard, 24GeneTests, 31ICD10 via Orphanet, 37MedGen, 39MeSH, 40MESH via Orphanet, 48NIH Rare Diseases, 50Novoseek, 52OMIM, 54Orphanet, 64The Human Phenotype Ontology, 68UMLS, 69UMLS via Orphanet, 70UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Wolcott-Rallison Syndrome:

Name: Wolcott-Rallison Syndrome 52 24 54 70 12 50 68
Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus 24 70
Med-Iddm Syndrome 48 70
Iddm-Med Syndrome 48 70
Wrs 54 70
 
Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus 52
Epiphyseal Dysplasia Multiple with Early-Onset Diabetes Mellitus 48
Early-Onset Diabetes Mellitus with Multiple Epiphyseal Dysplasia 54
Wolcott Rallison Syndrome 48

Characteristics:

Orphanet epidemiological data:

54
wolcott-rallison syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

64
wolcott-rallison syndrome:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset
Mortality/Aging: death in infancy

Classifications:



External Ids:

OMIM52 226980
Orphanet54 ORPHA1667
MESH via Orphanet40 C536739
UMLS via Orphanet69 C0432217
ICD10 via Orphanet31 E13
MedGen37 C0432217
MeSH39 D010009

Summaries for Wolcott-Rallison Syndrome

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OMIM:52 Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by permanent neonatal or early infancy... (226980) more...

MalaCards based summary: Wolcott-Rallison Syndrome, also known as multiple epiphyseal dysplasia with early-onset diabetes mellitus, is related to and long qt syndrome 1, and has symptoms including Array, Array and Array. An important gene associated with Wolcott-Rallison Syndrome is EIF2AK3 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3), and among its related pathways are Translational Control and Unfolded Protein Response (UPR). Affiliated tissues include bone, pancreas and liver.

UniProtKB/Swiss-Prot:70 Wolcott-Rallison syndrome: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities.

Related Diseases for Wolcott-Rallison Syndrome

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Diseases related to Wolcott-Rallison Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 18)
idRelated DiseaseScoreTop Affiliating Genes
111.2
2long qt syndrome 110.8
3neonatal diabetes mellitus10.3
4hypothyroidism10.3
5acute liver failure10.1
6hepatitis10.1
7liver disease10.1
8hypoaldosteronism10.1
9spinal muscular atrophy9.9
10muscular atrophy9.9
11distal muscular dystrophy9.8EIF2AK3, KCNJ5
12malaria9.7
13prostate cancer9.7
14cutaneous leishmaniasis9.7
15plasmodium vivax malaria9.7
16prostatitis9.7
17leishmaniasis9.7
18interleukin 1 receptor antagonist deficiency9.3EIF2AK3, EIF2S1, KCNJ5, PAX4

Graphical network of diseases related to Wolcott-Rallison Syndrome:



Diseases related to wolcott-rallison syndrome

Symptoms & Phenotypes for Wolcott-Rallison Syndrome

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Symptoms by clinical synopsis from OMIM:

226980

Clinical features from OMIM:

226980

Human phenotypes related to Wolcott-Rallison Syndrome:

 54 64 (show all 83)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 renal tubular dysfunction64 54 Very frequent (99-80%) HP:0000124
2 thin vermilion border64 54 Very frequent (99-80%) HP:0000233
3 epicanthus64 54 Very frequent (99-80%) HP:0000286
4 triangular face64 54 Very frequent (99-80%) HP:0000325
5 high forehead64 54 Very frequent (99-80%) HP:0000348
6 hypermetropia64 54 Very frequent (99-80%) HP:0000540
7 microdontia64 54 Very frequent (99-80%) HP:0000691
8 osteopenia64 54 Very frequent (99-80%) HP:0000938
9 osteoporosis64 54 Very frequent (99-80%) HP:0000939
10 abnormality of the metaphyses64 54 Very frequent (99-80%) HP:0000944
11 death in infancy54 Very frequent (99-80%)
12 weight loss64 54 Very frequent (99-80%) HP:0001824
13 dehydration64 54 Very frequent (99-80%) HP:0001944
14 hyperuricemia64 54 Very frequent (99-80%) HP:0002149
15 steatorrhea64 54 Very frequent (99-80%) HP:0002570
16 multiple epiphyseal dysplasia64 54 Very frequent (99-80%) HP:0002654
17 epiphyseal dysplasia64 54 Very frequent (99-80%) HP:0002656
18 hyperglycemia64 54 Very frequent (99-80%) HP:0003074
19 glycosuria64 54 Very frequent (99-80%) HP:0003076
20 short stature64 54 Very frequent (99-80%) HP:0004322
21 abnormality of epiphysis morphology54 Very frequent (99-80%)
22 transient neonatal diabetes mellitus64 54 Very frequent (99-80%) HP:0008255
23 cone-shaped epiphyses of the phalanges of the hand64 54 Very frequent (99-80%) HP:0010230
24 abnormality of pancreas morphology54 Very frequent (99-80%)
25 platyspondyly64 54 Frequent (79-30%) HP:0000926
26 brachydactyly syndrome64 54 Frequent (79-30%) HP:0001156
27 intellectual disability64 54 Frequent (79-30%) HP:0001249
28 muscular hypotonia64 54 Frequent (79-30%) HP:0001252
29 motor delay64 54 Frequent (79-30%) HP:0001270
30 gait disturbance64 54 Frequent (79-30%) HP:0001288
31 abnormal heart morphology64 54 Frequent (79-30%) HP:0001627
32 neutropenia64 54 Frequent (79-30%) HP:0001875
33 ketoacidosis64 54 Frequent (79-30%) HP:0001993
34 hepatomegaly64 54 Frequent (79-30%) HP:0002240
35 coxa valga64 54 Frequent (79-30%) HP:0002673
36 delayed skeletal maturation64 54 Frequent (79-30%) HP:0002750
37 hip dislocation64 54 Frequent (79-30%) HP:0002827
38 genu valgum64 54 Frequent (79-30%) HP:0002857
39 narrow iliac wings64 54 Frequent (79-30%) HP:0002868
40 elevated hepatic transaminases64 54 Frequent (79-30%) HP:0002910
41 acute hepatic failure64 54 Frequent (79-30%) HP:0006554
42 intracerebral periventricular calcifications64 54 Frequent (79-30%) HP:0007229
43 short thorax64 54 Frequent (79-30%) HP:0010306
44 neurodevelopmental delay54 Frequent (79-30%)
45 enlarged thorax64 54 Frequent (79-30%) HP:0100625
46 chronic hepatic failure64 54 Frequent (79-30%) HP:0100626
47 renal insufficiency64 54 Occasional (29-5%) HP:0000083
48 nephropathy64 54 Occasional (29-5%) HP:0000112
49 microcephaly64 54 Occasional (29-5%) HP:0000252
50 hypothyroidism64 54 Occasional (29-5%) HP:0000821
51 jaundice64 54 Occasional (29-5%) HP:0000952
52 seizures64 54 Occasional (29-5%) HP:0001250
53 intrauterine growth retardation64 54 Occasional (29-5%) HP:0001511
54 exocrine pancreatic insufficiency64 54 Occasional (29-5%) HP:0001738
55 hypoglycemia64 54 Occasional (29-5%) HP:0001943
56 abnormality of neuronal migration64 54 Occasional (29-5%) HP:0002269
57 pancreatic hypoplasia64 54 Occasional (29-5%) HP:0002594
58 recurrent fractures64 54 Occasional (29-5%) HP:0002757
59 kyphosis64 54 Occasional (29-5%) HP:0002808
60 hyperlordosis64 54 Occasional (29-5%) HP:0003307
61 reduced pancreatic beta cells64 54 Occasional (29-5%) HP:0006274
62 coma64 54 Very rare (<4-1%) HP:0001259
63 high palate64 HP:0000218
64 hypertelorism64 HP:0000316
65 upslanted palpebral fissure64 HP:0000582
66 insulin-resistant diabetes mellitus64 HP:0000831
67 global developmental delay64 HP:0001263
68 hypertonia64 HP:0001276
69 carpal bone hypoplasia64 HP:0001498
70 barrel-shaped chest64 HP:0001552
71 flattened epiphysis64 HP:0003071
72 irregular vertebral endplates64 HP:0003301
73 hypoplasia of the odontoid process64 HP:0003311
74 irregular carpal bones64 HP:0004236
75 preauricular pit64 HP:0004467
76 depressed nasal bridge64 HP:0005280
77 shortening of all middle phalanges of the fingers64 HP:0006110
78 irregular tarsal ossification64 HP:0008134
79 ivory epiphyses of the toes64 HP:0010168
80 ivory epiphyses of the phalanges of the hand64 HP:0010234
81 small epiphyses64 HP:0010585
82 hip subluxation64 HP:0030043
83 type i diabetes mellitus64 HP:0100651

Drugs & Therapeutics for Wolcott-Rallison Syndrome

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Wolcott-Rallison Syndrome

Genetic Tests for Wolcott-Rallison Syndrome

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Genetic tests related to Wolcott-Rallison Syndrome:

id Genetic test Affiliating Genes
1 Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus24 EIF2AK3

Anatomical Context for Wolcott-Rallison Syndrome

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MalaCards organs/tissues related to Wolcott-Rallison Syndrome:

36
Bone, Pancreas, Liver, Heart, Kidney

Publications for Wolcott-Rallison Syndrome

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Articles related to Wolcott-Rallison Syndrome:

(show all 33)
idTitleAuthorsYear
1
Novel splice site mutation in EIF2AK3 gene causes Wolcott-Rallison syndrome in a consanguineous family from Saudi Arabia. (28220546)
2017
2
En bloc multiorgan transplant (liver, pancreas, and kidney) for acute liver and renal failure in a patient with wolcott-rallison syndrome. (26784269)
2016
3
Wolcott-Rallison syndrome with novel EIF2AK3 gene mutation. (27145240)
2016
4
Os odontoideum in wolcott-rallison syndrome: a case series of 4 patients. (26860746)
2016
5
Anaesthesia and orphan disease: a child with Wolcott-Rallison syndrome. (25101713)
2015
6
Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort. (25659842)
2015
7
Novel mutation in wolcott-rallison syndrome with variable expression in two omani siblings. (25960841)
2015
8
RelatA+ve hypoaldosteronism in a patient with Wolcott-Rallison syndrome. (26433138)
2015
9
Liver, pancreas and kidney transplantation for the treatment of Wolcott-Rallison syndrome. (25384546)
2015
10
Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek case of Wolcott-Rallison syndrome. (24859506)
2014
11
Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases. (25131821)
2014
12
Wolcott Rallison syndrome: a rare inherited diabetes mellitus. (24710710)
2014
13
Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review. (28156240)
2013
14
Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome. (24194294)
2013
15
Primary hypothyroidism: an unusual manifestation of Wolcott-Rallison syndrome. (23933668)
2013
16
Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review. (23759358)
2013
17
EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome. (24168455)
2013
18
Variable phenotype in five patients with Wolcott-Rallison syndrome due to the same EIF2AK3 (c.1259delA) mutation. (23585173)
2013
19
Recurrent Hepatitis in Two Iranian Children: A Novel (Q166R) Mutation in EIF2AK3 Leading to Wolcott-Rallison Syndrome. (24032041)
2013
20
Wolcott-Rallison syndrome due to a novel mutation (R491X) in EIF2AK3 gene. (22672868)
2012
21
Wolcott-Rallison syndrome. (23263430)
2012
22
A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child. (21648287)
2011
23
Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome. (21518408)
2011
24
Wolcott-Rallison syndrome. (21050479)
2010
25
Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. (20202148)
2010
26
Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. (19837917)
2009
27
Recurrent acute liver failure and mitochondriopathy in a case of Wolcott-Rallison syndrome. (18704764)
2008
28
A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott-Rallison syndrome. (16813601)
2006
29
Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. (15220213)
2004
30
Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature. (15384883)
2004
31
Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. (12086964)
2002
32
EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. (10932183)
2000
33
Organisation of the human PAX4 gene and its exclusion as a candidate for the Wolcott-Rallison syndrome. (9598721)
1998

Variations for Wolcott-Rallison Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Wolcott-Rallison Syndrome:

70
id Symbol AA change Variation ID SNP ID
1EIF2AK3p.Arg588GlnVAR_011408rs121908569

Clinvar genetic disease variations for Wolcott-Rallison Syndrome:

5
id Gene Variation Type Significance SNP ID Assembly Location
1EIF2AK3NM_ 004836.6(EIF2AK3): c.1192C> T (p.Gln398Ter)SNVPathogenicrs864621972GRCh37Chr 2, 88888393: 88888393
2EIF2AK3NM_ 004836.6(EIF2AK3): c.1564_ 1565delTG (p.Trp522Glufs)deletionPathogenicrs797045558GRCh38Chr 2, 88585926: 88585927
3EIF2AK3NM_ 004836.6(EIF2AK3): c.1035dupT (p.Lys346Terfs)duplicationPathogenicrs869025178GRCh37Chr 2, 88890091: 88890091
4EIF2AK3NM_ 004836.6(EIF2AK3): c.1763G> A (p.Arg588Gln)SNVPathogenicrs121908569GRCh37Chr 2, 88882948: 88882948
5EIF2AK3NM_ 004836.6(EIF2AK3): c.2985+1G> ASNVPathogenicrs869025179GRCh37Chr 2, 88870391: 88870391
6EIF2AK3EIF2AK3, 4-BP DEL, 1563GAAAdeletionPathogenic
7EIF2AK3NM_ 004836.6(EIF2AK3): c.994G> T (p.Glu332Ter)SNVPathogenicrs121908570GRCh37Chr 2, 88890344: 88890344

Expression for genes affiliated with Wolcott-Rallison Syndrome

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Search GEO for disease gene expression data for Wolcott-Rallison Syndrome.

Pathways for genes affiliated with Wolcott-Rallison Syndrome

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GO Terms for genes affiliated with Wolcott-Rallison Syndrome

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Biological processes related to Wolcott-Rallison Syndrome according to GeneCards Suite gene sharing:

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1cellular response to amino acid starvationGO:003419810.1EIF2AK3, EIF2S1
2negative regulation of translational initiation in response to stressGO:003205710.1EIF2AK3, EIF2S1
3PERK-mediated unfolded protein responseGO:003649910.1EIF2AK3, EIF2S1
4protein autophosphorylationGO:004677710.0EIF2AK3, EIF2S1
5endocrine pancreas developmentGO:003101810.0EIF2AK3, PAX4
6regulation of translationGO:00064179.9EIF2AK3, EIF2S1
7response to endoplasmic reticulum stressGO:00349769.4EIF2AK3, EIF2S1
8response to manganese-induced endoplasmic reticulum stressGO:19907379.4EIF2AK3, EIF2S1

Sources for Wolcott-Rallison Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet