MCID: ART062
MIFTS: 51

Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Categories: Genetic diseases, Rare diseases, Nephrological diseases

Aliases & Classifications for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

MalaCards integrated aliases for Arthrogryposis, Renal Dysfunction, and Cholestasis 1:

Name: Arthrogryposis, Renal Dysfunction, and Cholestasis 1 53 13
Arc Syndrome 53 12 72 49 71 14
Arthrogryposis Renal Dysfunction Cholestasis Syndrome 72 49 28 69
Renal Insufficiency 41 69 28
Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome 72 49
Arthrogryposis, Renal Dysfunction, and Cholestasis 12 36
Arcs1 53 71
Arcs 53 71
Arthrogryposis Multiplex Congenita, Renal Dysfunction, and Cholestasis 49
Arthrogryposis, Renal Dysfunction and Cholestasis Syndrome 12
Arthrogryposis, Renal Dysfunction and Cholestasis Syndrome 1 71
Arthrogryposis Renal Dysfunction and Cholestasis 1 71
Arthrogryposis - Renal Dysfunction - Cholestasis 49
Arthrogryposis-Renal Dysfunction-Cholestasis 12
Arc Syndrome; Arcs 53
Kidney Failure 69

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
death in infancy, usually from sepsis, dehydration, or acidosis


HPO:

31
arthrogryposis, renal dysfunction, and cholestasis 1:
Mortality/Aging death in infancy
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Disease Ontology : 12 A syndrome that is characterized by congenital joint contractures, renal tubular dysfunction, cholestasis, severe failure to thrive, ichthyosis, and a defect in platelet alpha-granule biogenesis. It has material basis in homozygous or compound heterozygous mutation in the VPS33B gene or has masterial basis in homozygous or compound heterozygous mutation in the VIPAR gene on chromosome 14q24.3.

MalaCards based summary : Arthrogryposis, Renal Dysfunction, and Cholestasis 1, also known as arc syndrome, is related to cholestasis and arthrogryposis, renal dysfunction, and cholestasis 2, and has symptoms including low-set ears, failure to thrive and global developmental delay. An important gene associated with Arthrogryposis, Renal Dysfunction, and Cholestasis 1 is VPS33B (VPS33B, Late Endosome And Lysosome Associated). The drugs Artesunate and Anti-Infective Agents have been mentioned in the context of this disorder. Affiliated tissues include kidney, liver and testes.

NIH Rare Diseases : 49 This condition doesn't have a summary yet. Please see our page(s) on Arthrogryposis multiplex congenita.

UniProtKB/Swiss-Prot : 71 Arthrogryposis, renal dysfunction and cholestasis syndrome 1: A multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase activity. Platelet dysfunction is common.

Description from OMIM: 208085

Related Diseases for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Diseases in the Arthrogryposis, Renal Dysfunction, and Cholestasis 1 family:

Arthrogryposis, Renal Dysfunction, and Cholestasis 2

Diseases related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 243)
# Related Disease Score Top Affiliating Genes
1 cholestasis 29.9 VIPAS39 VPS33B
2 arthrogryposis, renal dysfunction, and cholestasis 2 11.9
3 secondary hyperparathyroidism of renal origin 11.3
4 papillorenal syndrome 11.3
5 focal segmental glomerulosclerosis 1 11.1
6 nephrolithiasis, x-linked recessive, with renal failure 11.0
7 tafro syndrome 10.9
8 amyloidosis, hereditary, transthyretin-related 10.9
9 fanconi renotubular syndrome 1 10.9
10 dent disease 1 10.9
11 hypophosphatemic rickets, x-linked recessive 10.9
12 proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis 10.9
13 nephrotic syndrome, type 7 10.9
14 autosomal dominant tubulointerstitial kidney disease 10.9
15 exudative vitreoretinopathy 1 10.8
16 exudative vitreoretinopathy 2, x-linked 10.8
17 exudative vitreoretinopathy 4 10.8
18 exudative vitreoretinopathy 5 10.8
19 exudative vitreoretinopathy 6 10.8
20 exudative vitreoretinopathy 7 10.8
21 photokeratitis 10.8
22 preretinal fibrosis 10.8
23 toxic pneumonitis 10.8
24 vesicoureteral reflux 1 10.8
25 polycystic kidney disease 4 with or without hepatic disease 10.8
26 mental retardation, x-linked, syndromic, martin-probst type 10.8
27 dent disease 2 10.8
28 polycystic kidney disease 3 10.8
29 focal segmental glomerulosclerosis 2 10.8
30 focal segmental glomerulosclerosis 3 10.8
31 congenital anomalies of kidney and urinary tract 1 10.8
32 vesicoureteral reflux 2 10.8
33 focal segmental glomerulosclerosis 4 10.8
34 focal segmental glomerulosclerosis 5 10.8
35 fanconi renotubular syndrome 2 10.8
36 vesicoureteral reflux 3 10.8
37 focal segmental glomerulosclerosis 6 10.8
38 fanconi renotubular syndrome 3 10.8
39 vesicoureteral reflux 8 10.8
40 focal segmental glomerulosclerosis 7 10.8
41 focal segmental glomerulosclerosis 8 10.8
42 focal segmental glomerulosclerosis 9 10.8
43 iga nephropathy 3 10.8
44 renal tubular acidosis 10.8
45 kleefstra syndrome 10.8
46 hepatic veno-occlusive disease 10.8
47 retinitis pigmentosa-intellectual disability-deafness-hypogonadism syndrome 10.8
48 neural tube defects 10.4
49 arthrogryposis multiplex congenita, neurogenic, with myelin defect 10.1
50 kidney disease 10.0

Graphical network of the top 20 diseases related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1:



Diseases related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Symptoms & Phenotypes for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Symptoms via clinical synopsis from OMIM:

53
HeadAndNeckEars:
low-set ears

NeurologicCentralNervousSystem:
global developmental delay
hypotonia
lissencephaly (reported in 1 patient)

HeadAndNeckHead:
microcephaly

GenitourinaryKidneys:
nephropathy
nephrocalcinosis
renal tubular acidosis
fanconi syndrome
nephrogenic diabetes insipidus (less common)
more
AbdomenLiver:
cholestatic liver disease
bile duct abnormalities (paucity, proliferation)
giant cell hepatitis
pigmentary deposits
portal tract fibrosis

MetabolicFeatures:
metabolic acidosis

SkeletalFeet:
talipes calcaneovalgus

Hematology:
severe bleeding after biopsies (uncommon)

GrowthOther:
failure to thrive

SkeletalPelvis:
hip dysplasia

SkinNailsHairSkin:
ichthyosis
jaundice

HeadAndNeckFace:
micrognathia
sloping forehead

Skeletal:
arthrogryposis multiplex congenita
fractures at birth

LaboratoryAbnormalities:
conjugated hyperbilirubinemia
abnormal liver function tests

CardiovascularHeart:
atrial septal defects
ventricular septal defects
structural cardiac defects (uncommon)
persistent foramen ovale
right ventricular hypertrophy (reported in 2 sibs)

Immunology:
recurrent febrile illnesses
b and t cell defects (reported in 2 sibs)


Clinical features from OMIM:

208085

Human phenotypes related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1:

31 (show all 27)
# Description HPO Frequency HPO Source Accession
1 low-set ears 31 HP:0000369
2 failure to thrive 31 HP:0001508
3 global developmental delay 31 HP:0001263
4 hip dysplasia 31 HP:0001385
5 microcephaly 31 HP:0000252
6 ichthyosis 31 HP:0008064
7 nephropathy 31 HP:0000112
8 dehydration 31 HP:0001944
9 nephrogenic diabetes insipidus 31 occasional (7.5%) HP:0009806
10 micrognathia 31 HP:0000347
11 abnormal bleeding 31 occasional (7.5%) HP:0001892
12 elevated hepatic transaminases 31 HP:0002910
13 atrial septal defect 31 HP:0001631
14 cholestatic liver disease 31 HP:0002611
15 jaundice 31 HP:0000952
16 arthrogryposis multiplex congenita 31 HP:0002804
17 ventricular septal defect 31 HP:0001629
18 nephrocalcinosis 31 HP:0000121
19 metabolic acidosis 31 HP:0001942
20 sloping forehead 31 HP:0000340
21 lissencephaly 31 occasional (7.5%) HP:0001339
22 generalized hypotonia 31 HP:0001290
23 conjugated hyperbilirubinemia 31 HP:0002908
24 renal tubular acidosis 31 HP:0001947
25 talipes calcaneovalgus 31 HP:0001884
26 right ventricular hypertrophy 31 HP:0001667
27 giant cell hepatitis 31 HP:0200084

UMLS symptoms related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1:


icterus

Drugs & Therapeutics for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Drugs for Arthrogryposis, Renal Dysfunction, and Cholestasis 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Artesunate Approved, Investigational 88495-63-0 5464098 6917864
2 Anti-Infective Agents
3 Antimalarials
4 Antiparasitic Agents
5 Antiprotozoal Agents
6 Artemisinine
7 Artemisinins

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Artemisinin Resistance in Cambodia II Completed NCT00722150 Artesunate;Artesunate;Artesunate
2 Family Meal Duration and Children's Eating Behavior Recruiting NCT03127579

Search NIH Clinical Center for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Cochrane evidence based reviews: renal insufficiency

Genetic Tests for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Genetic tests related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1:

# Genetic test Affiliating Genes
1 Arthrogryposis Renal Dysfunction Cholestasis Syndrome 28 VPS33B
2 Renal Insufficiency 28

Anatomical Context for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

MalaCards organs/tissues related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1:

38
Kidney, Liver, Testes, T Cells

Publications for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Articles related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1:

(show all 30)
# Title Authors Year
1
The Role of Platelets and I/-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage. ( 26505894 )
2015
2
ARC syndrome with high GGT cholestasis caused by VPS33B mutations. ( 24782640 )
2014
3
ArthrogryposisA?renal dysfunctionA?cholestasis (ARC) syndrome: from molecular genetics to clinical features. ( 25239142 )
2014
4
Haematological manifestations of arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome: a case report. ( 23622807 )
2013
5
ARC syndrome in preterm baby. ( 24071963 )
2013
6
ARC Syndrome Due to VIPAR Mutation is Another Cause of Neonatal Cholestasis with Normal Serum Gammaglutamyl Transferase Activity. ( 23636179 )
2013
7
ARC syndrome with complex renal problems: nephrocalcinosis, proximal and hyperkalemic distal RTA and nephrogenic diabetes insipidus. ( 22805396 )
2012
8
Associations among genotype, clinical phenotype, and intracellular localization of trafficking proteins in ARC syndrome. ( 22753090 )
2012
9
Agranular platelets as a cardinal feature of ARC syndrome. ( 20224444 )
2010
10
Arc syndrome without arthrogryposis, with hip dislocation and renal glomerulocystic appearance: a case report. ( 18972129 )
2009
11
Clinical characteristics and VPS33B mutations in patients with ARC syndrome. ( 19274792 )
2009
12
Molecular investigations to improve diagnostic accuracy in patients with ARC syndrome. ( 18853461 )
2009
13
A novel VPS33B mutation in an ARC syndrome patient presenting with osteopenia and fractures at birth. ( 17994566 )
2007
14
VPS33B mutation with ichthyosis, cholestasis, and renal dysfunction but without arthrogryposis: incomplete ARC syndrome phenotype. ( 16492441 )
2006
15
Clinical and molecular genetic features of ARC syndrome. ( 16896922 )
2006
16
Increased nuchal translucency in arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome and discovery of a Portuguese specific mutation in the VPS33B gene. ( 16758438 )
2006
17
ARC syndrome. ( 15981766 )
2005
18
Arthrogryposis, renal tubular acidosis and cholestasis (ARC) syndrome: two new cases and review. ( 16155421 )
2005
19
Ichthyosis associated with ARC syndrome: ARC syndrome is one of the differential diagnoses of ichthyosis. ( 16354257 )
2005
20
Liver biopsy complicated by hemorrhage in a patient with ARC syndrome. ( 15500499 )
2004
21
Mutations in VPS33B, encoding a regulator of SNARE-dependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome. ( 15052268 )
2004
22
ARC syndrome: an expanding range of phenotypes. ( 12138079 )
2002
23
ARC syndrome is not so rare. ( 11897818 )
2002
24
ARC syndrome: an expanding range of phenotypes. ( 11668108 )
2001
25
Cerebral defects and nephrogenic diabetes insipidus with the ARC syndrome: additional findings or a new syndrome (ARCC-NDI)? ( 9332665 )
1997
26
Liver histology in the arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC) syndrome: report of three new cases and review. ( 8151641 )
1994
27
The four-in-one arthroplasty for the painful arc syndrome. ( 7067240 )
1982
28
Subacromial bursitis with loose bodies as a cause of refractory painful-arc syndrome. A case report. ( 7430208 )
1980
29
The refractory painful arc syndrome. ( 711806 )
1978
30
The painful arc syndrome. Clinical classification as a guide to management. ( 873977 )
1977

Variations for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

UniProtKB/Swiss-Prot genetic disease variations for Arthrogryposis, Renal Dysfunction, and Cholestasis 1:

71
# Symbol AA change Variation ID SNP ID
1 VPS33B p.Leu30Pro VAR_018983 rs121434385
2 VPS33B p.Ser243Phe VAR_057901 rs139829189

ClinVar genetic disease variations for Arthrogryposis, Renal Dysfunction, and Cholestasis 1:

6 (show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 TSC1 NM_000368.4(TSC1): c.989dupT (p.Ser331Glufs) duplication Pathogenic rs118203478 GRCh37 Chromosome 9, 135786880: 135786880
2 VPS33B NM_018668.3(VPS33B): c.240-577_290-156del deletion Pathogenic GRCh37 Chromosome 15, 91557257: 91558240
3 VPS33B NM_018668.4(VPS33B): c.1225+5G> C single nucleotide variant Pathogenic rs398122407 GRCh37 Chromosome 15, 91548102: 91548102
4 VPS33B NM_018668.4(VPS33B): c.1261_1262delCA (p.Gln421Valfs) deletion Pathogenic rs398122408 GRCh37 Chromosome 15, 91546325: 91546326
5 VPS33B NM_018668.4(VPS33B): c.1594C> T (p.Arg532Ter) single nucleotide variant Pathogenic rs121434383 GRCh37 Chromosome 15, 91543193: 91543193
6 VPS33B NM_018668.4(VPS33B): c.1312C> T (p.Arg438Ter) single nucleotide variant Pathogenic rs121434384 GRCh37 Chromosome 15, 91545373: 91545373
7 VPS33B NM_018668.4(VPS33B): c.89T> C (p.Leu30Pro) single nucleotide variant Pathogenic rs121434385 GRCh37 Chromosome 15, 91565391: 91565391
8 VPS33B NM_018668.4(VPS33B): c.700+1G> A single nucleotide variant Pathogenic rs794726658 GRCh38 Chromosome 15, 91006949: 91006949
9 VPS33B NM_018668.4(VPS33B): c.1616delA (p.Glu539Glyfs) deletion Pathogenic rs886043445 GRCh37 Chromosome 15, 91543171: 91543171
10 VPS33B NM_018668.4(VPS33B): c.403+2T> A single nucleotide variant Pathogenic rs769333468 GRCh38 Chromosome 15, 91009799: 91009799
11 VPS33B NM_018668.4(VPS33B): c.1498G> T (p.Glu500Ter) single nucleotide variant Pathogenic rs751858602 GRCh38 Chromosome 15, 91000573: 91000573

Expression for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Search GEO for disease gene expression data for Arthrogryposis, Renal Dysfunction, and Cholestasis 1.

Pathways for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

GO Terms for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

Cellular components related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 cytoplasmic vesicle GO:0031410 9.81 VIPAS39 VPS16 VPS33A VPS33B
2 endosome GO:0005768 9.8 TGFBRAP1 VIPAS39 VPS16 VPS33A VPS33B VPS39
3 lysosome GO:0005764 9.76 VPS16 VPS33A VPS33B VPS39
4 lysosomal membrane GO:0005765 9.73 VPS16 VPS33A VPS33B VPS39
5 recycling endosome GO:0055037 9.67 VIPAS39 VPS16 VPS33B
6 late endosome membrane GO:0031902 9.67 VPS16 VPS33A VPS33B VPS39
7 early endosome GO:0005769 9.65 TGFBRAP1 VIPAS39 VPS16 VPS33A VPS33B
8 clathrin-coated vesicle GO:0030136 9.58 VPS16 VPS33A VPS33B
9 autophagosome GO:0005776 9.52 VPS16 VPS33A
10 clathrin complex GO:0071439 9.48 VPS33A VPS33B
11 late endosome GO:0005770 9.35 VIPAS39 VPS16 VPS33A VPS33B VPS39
12 AP-3 adaptor complex GO:0030123 9.33 VPS33A VPS33B VPS39
13 HOPS complex GO:0030897 9.02 VIPAS39 VPS16 VPS33A VPS33B VPS39

Biological processes related to Arthrogryposis, Renal Dysfunction, and Cholestasis 1 according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.93 TGFBRAP1 VIPAS39 VPS16 VPS33A VPS33B VPS39
2 protein transport GO:0015031 9.73 TGFBRAP1 VIPAS39 VPS16 VPS33A VPS33B VPS39
3 autophagy GO:0006914 9.67 VPS16 VPS33A VPS39
4 vesicle-mediated transport GO:0016192 9.62 TGFBRAP1 VPS33A VPS33B VPS39
5 collagen fibril organization GO:0030199 9.55 VIPAS39 VPS33B
6 intracellular protein transport GO:0006886 9.55 TGFBRAP1 VIPAS39 VPS16 VPS33B VPS39
7 vesicle docking involved in exocytosis GO:0006904 9.54 VPS33A VPS33B
8 lysosome localization GO:0032418 9.52 VPS33A VPS33B
9 platelet formation GO:0030220 9.51 NBEAL2 VPS33A
10 collagen metabolic process GO:0032963 9.48 VIPAS39 VPS33B
11 endosomal vesicle fusion GO:0034058 9.43 TGFBRAP1 VPS39
12 peptidyl-lysine hydroxylation GO:0017185 9.4 VIPAS39 VPS33B
13 melanosome localization GO:0032400 9.37 VPS33A VPS33B
14 autophagosome maturation GO:0097352 9.26 VIPAS39 VPS16 VPS33A VPS33B
15 endosome to lysosome transport GO:0008333 9.1 TGFBRAP1 VIPAS39 VPS16 VPS33A VPS33B VPS39

Sources for Arthrogryposis, Renal Dysfunction, and Cholestasis 1

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
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