OHST
MCID: OVR093
MIFTS: 40

Overhydrated Hereditary Stomatocytosis (OHST)

Categories: Blood diseases, Genetic diseases, Liver diseases, Rare diseases

Aliases & Classifications for Overhydrated Hereditary Stomatocytosis

MalaCards integrated aliases for Overhydrated Hereditary Stomatocytosis:

Name: Overhydrated Hereditary Stomatocytosis 57 53 59 74 37 55
Stomatocytosis I 53 29 13 6 72
Potassium Sodium Disorder of Erythrocyte 53 74
Ohst 57 74
Ohs 57 74
Hereditary, Overhydrated, Cation-Leak Stomatocytosis 74
Potassium-Sodium Disorder of Erythrocyte 57
Overhydrated Cation Leak Stomatocytosis 74
Stomatocytosis, Overhydrated Hereditary 40

Characteristics:

Orphanet epidemiological data:

59
overhydrated hereditary stomatocytosis
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
some patients experience respiratory infections in association with episodes of jaundice in childhood


HPO:

32
overhydrated hereditary stomatocytosis:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 185000
KEGG 37 H01979
MeSH 44 D000745
ICD10 via Orphanet 34 D58.8
Orphanet 59 ORPHA3203
MedGen 42 C1861455
UMLS 72 C1861455

Summaries for Overhydrated Hereditary Stomatocytosis

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 3203DefinitionOverhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia.EpidemiologyOHSt is very rare with only seven cases described in the literature so far.Clinical descriptionOnset occurs during the neonatal period or infancy with hemolytic anemia that may require occasional blood transfusions. Splenomegaly or hepatosplenomegaly are present. The disease course is marked by the usual complications of hemolytic anemia (biliary lithiasis) and, remarkably, by a strong tendency for iron overload.EtiologyIn the majority of cases, OHSt is caused by mutations in the RHAG gene (6p21-qter) encoding the Rh-associated glycoprotein component of the Rh complex.Diagnostic methodsDiagnosis is based on a massive right shift of the osmotic gradient ektacytometry curve indicating overhydrated red cells and decreased osmotic resistance, together with a substantial increase in the monovalent cation leak compared to controls, and a sharp decrease of the leak as a function of decreasing temperature. Blood smears show an elevated percentage of well formed stomatocytes. There is macrocytosis, a low mean cell hemoglobin concentration (MCHC) and a high reticulocyte count. Electrophoresis reveals that the membrane protein stomatin is absent or present at only low levels.Differential diagnosisThe differential diagnosis should include the most common form of hereditary stomatocytosis, dehydrated hereditary stomatocytosis, as well as hereditary cryohydrocytosis with reduced stomatin (see these terms).Genetic counselingOHSt is transmitted as an autosomal dominant trait but de novo mutations are quite common.Management and treatmentTreatment involves blood transfusions, when necessary, together with management of biliary lithiasis and iron overload. Splenectomy is contraindicated in OHSt patients as it may induce venous thromboembolic complications.PrognosisWith correct management of the complications, the prognosis is good.Visit the Orphanet disease page for more resources.

MalaCards based summary : Overhydrated Hereditary Stomatocytosis, also known as stomatocytosis i, is related to hemolytic anemia and occipital horn syndrome, and has symptoms including icterus An important gene associated with Overhydrated Hereditary Stomatocytosis is RHAG (Rh Associated Glycoprotein), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and Ion channel transport. Affiliated tissues include spleen, and related phenotypes are splenomegaly and hepatomegaly

OMIM : 57 Overhydrated hereditary stomatocytosis is a variably compensated macrocytic hemolytic anemia of fluctuating severity, characterized by circulating erythrocytes with slit-like lucencies (stomata) evident on peripheral blood smears. OHST red cells exhibit cation leak, resulting in elevated cell Na+ content with reduced K+ content, with increased ouabain-resistant cation leak fluxes in the presence of presumably compensatory increases in ouabain-sensitive Na(+)-K(+) ATPase activity, and red cell age-dependent loss of stomatin/EBP7.2 (EBP72; 133090) from the erythroid membrane. Clinically, patients with OHST exhibit overhydrated erythrocytes and a temperature-dependent red cell cation leak. The temperature dependence of the leak is 'monotonic' and has a steep slope, reflecting the very large leak at 37 degrees centigrade (summary by Bruce, 2009 and Stewart et al., 2011). For a discussion of clinical and genetic heterogeneity of the hereditary stomatocytoses, see 194380. (185000)

KEGG : 37
Overhydrated hereditary stomatocytosis (OHST), which is clinically characterized by a hemolytic anemia, is a rare, dominantly inherited disorder of red blood cells (RBCs) associated with increased membrane permeability to monovalent cations and increased activity of the Na+K+-ATPase. The influx of Na+ exceeds the loss of K+ causing water influx and resulting in swollen erythrocytes, hemolysis, and stomatocyte formation. The OHST phenotype is also associated with a dramatic decrease or the absence of the 32-kDa membrane raft protein stomatin. OHST diagnosis is based on a hemolytic anemia associated with a massive right shift of the osmotic gradient ektacytometry curve and a decreased osmotic resistance, together with a major increase in a monovalent cation leak. Recently, OHST was found to be linked to amino acid substitutions in Rh-associated glycoprotein (RhAG).

UniProtKB/Swiss-Prot : 74 Overhydrated hereditary stomatocytosis: An autosomal dominant disorder of red cell membrane permeability to monovalent cations, characterized by macrocytic hemolytic anemia of fluctuating severity, circulating erythrocytes with slit-like lucencies (stomata) evident on fixed, stained peripheral blood smears. OHST red cells exhibit cation leak, resulting in elevated cell sodium content with reduced potassium content. The disease is marked by splenomegaly or hepatosplenomegaly, cholelithiasis and a strong tendency for iron overload.

Related Diseases for Overhydrated Hereditary Stomatocytosis

Diseases related to Overhydrated Hereditary Stomatocytosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 529)
# Related Disease Score Top Affiliating Genes
1 hemolytic anemia 29.5 STOM RHAG
2 occipital horn syndrome 12.2
3 obesity-hypoventilation syndrome 11.8
4 dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema 11.6
5 rickets 11.5
6 bombay phenotype 11.5
7 back pain 11.5
8 hypophosphatemic rickets, x-linked dominant 11.5
9 adrenal hyperplasia, congenital, due to steroid 11-beta-hydroxylase deficiency 11.3
10 hermansky-pudlak syndrome 1 11.1
11 vitamin d hydroxylation-deficient rickets, type 1a 11.1
12 cardiogenic shock 11.1
13 hyperparathyroidism 10.6
14 hereditary stomatocytosis 10.6
15 secondary hyperparathyroidism 10.5
16 bone resorption disease 10.5
17 kidney disease 10.5
18 triiodothyronine receptor auxiliary protein 10.4
19 bone disease 10.4
20 osteogenic sarcoma 10.4
21 renal osteodystrophy 10.4
22 osteomalacia 10.3
23 osteoporosis 10.3
24 bone mineral density quantitative trait locus 8 10.3
25 bone mineral density quantitative trait locus 15 10.3
26 uremia 10.3
27 pertussis 10.3
28 chronic kidney disease 10.3
29 47,xyy 10.2
30 pain agnosia 10.2
31 rapidly involuting congenital hemangioma 10.2
32 breast cancer 10.2
33 hypophosphatemia 10.2
34 hypoparathyroidism 10.2
35 hyperphosphatemia 10.2
36 pustulosis of palm and sole 10.2
37 psoriasis 10.2
38 colorectal cancer 10.2
39 osteitis fibrosa 10.2
40 bone inflammation disease 10.2
41 48,xyyy 10.2
42 cytokine deficiency 10.2
43 autoimmune disease 10.1
44 dentinogenesis imperfecta type 2 10.1
45 hair whorl 10.1
46 leukemia, acute myeloid 10.1
47 metabolic acidosis 10.1
48 primary hyperparathyroidism 10.1
49 end stage renal failure 10.1
50 myeloid leukemia 10.1

Graphical network of the top 20 diseases related to Overhydrated Hereditary Stomatocytosis:



Diseases related to Overhydrated Hereditary Stomatocytosis

Symptoms & Phenotypes for Overhydrated Hereditary Stomatocytosis

Human phenotypes related to Overhydrated Hereditary Stomatocytosis:

32 (show all 9)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 32 HP:0001744
2 hepatomegaly 32 HP:0002240
3 hemolytic anemia 32 HP:0001878
4 jaundice 32 HP:0000952
5 reticulocytosis 32 HP:0001923
6 hyperbilirubinemia 32 HP:0002904
7 stomatocytosis 32 HP:0004446
8 increased red cell osmotic fragility 32 HP:0005502
9 increased intracellular sodium 32 HP:0003575

Symptoms via clinical synopsis from OMIM:

57
Abdomen Spleen:
splenomegaly

Hematology:
hemolytic anemia
reticulocytosis
stomatocytosis
increased osmotic fragility
elevated reticulocyte count
more
Laboratory Abnormalities:
hyperbilirubinemia

Abdomen Liver:
hepatomegaly
jaundice

Skin Nails Hair Skin:
jaundice

Clinical features from OMIM:

185000

UMLS symptoms related to Overhydrated Hereditary Stomatocytosis:


icterus

GenomeRNAi Phenotypes related to Overhydrated Hereditary Stomatocytosis according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased Sindbis virus (SIN) capsid and autophagosome LC3 protein colocalization GR00242-A-1 9.56 ANXA5 STOM
2 Decreased Sindbis virus (SIN) capsid and autophagosome LC3 protein colocalization GR00242-A-2 9.56 ANXA5 STOM
3 Decreased mitophagy mCherry-Parkin protein expression after carbonyl cyanide m-chlorphenylhydrazone (CCCP) stimulation GR00242-A-4 9.16 ANXA5 STOM
4 Decreased viability after sindbis virus (SIN) dsTE12Q infection GR00242-A-3 8.62 ANXA5 STOM

Drugs & Therapeutics for Overhydrated Hereditary Stomatocytosis

Search Clinical Trials , NIH Clinical Center for Overhydrated Hereditary Stomatocytosis

Genetic Tests for Overhydrated Hereditary Stomatocytosis

Genetic tests related to Overhydrated Hereditary Stomatocytosis:

# Genetic test Affiliating Genes
1 Stomatocytosis I 29 RHAG

Anatomical Context for Overhydrated Hereditary Stomatocytosis

MalaCards organs/tissues related to Overhydrated Hereditary Stomatocytosis:

41
Spleen

Publications for Overhydrated Hereditary Stomatocytosis

Articles related to Overhydrated Hereditary Stomatocytosis:

(show all 45)
# Title Authors PMID Year
1
The monovalent cation leak in overhydrated stomatocytic red blood cells results from amino acid substitutions in the Rh-associated glycoprotein. 38 8 71
18931342 2009
2
Autosomal dominant overhydrated stomatocytosis associated with the heterozygous RhAG mutation F65S: a case of missed heterozygosity due to allelic dropout. 8 71
23406318 2013
3
Loss-of-function and gain-of-function phenotypes of stomatocytosis mutant RhAG F65S. 8 71
21849667 2011
4
Four new cases of stomatin-deficient hereditary stomatocytosis syndrome: association of the stomatin-deficient cryohydrocytosis variant with neurological dysfunction. 8 71
15180870 2004
5
Hereditary stomatocytosis: consistent association with an integral membrane protein deficiency. 8 71
2765409 1989
6
Reduction of membrane band 7 and activation of volume stimulated (K+, Cl-)-cotransport in a case of congenital stomatocytosis. 8 71
2917122 1989
7
Hereditary stomatocytosis: membrane and metabolism studies. 8 71
1174702 1975
8
Stomatocytosis. 8 71
6018468 1967
9
Stomatocytosis: a hereditary red cell anomally associated with haemolytic anaemia. 8 71
13762977 1961
10
The "stomatin" gene and protein in overhydrated hereditary stomatocytosis. 9 38 8
12750157 2003
11
Human RhAG ammonia channel is impaired by the Phe65Ser mutation in overhydrated stomatocytic red cells. 38 71
22012326 2012
12
Hereditary stomatocytosis: phenotypical expression of sodium transport and band 7 peptides in 44 cases. 38 8
1419788 1992
13
Hereditary stomatocytosis and cation-leaky red cells--recent developments. 8
19261491 2009
14
A family showing recessively inherited multisystem pathology with aberrant splicing of the erythrocyte Band 7.2b ('stomatin') gene. 8
14970744 2004
15
Hereditary haemolytic anaemias and parvovirus infections in Jehovah's Witnesses. 8
12752115 2003
16
Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): mapping of locus to chromosome 16 (16q23-qter). 8
9718354 1998
17
Thrombo-embolic disease after splenectomy for hereditary stomatocytosis. 8
8639421 1996
18
Stomatin: a putative cation transport regulator in the red cell membrane. 8
7694657 1993
19
Integral band 7 protein of the human erythrocyte membrane. 8
1487064 1992
20
Congenital haemolytic anaemia in a low birth weight infant due to congenital stomatocytosis. 8
1868910 1991
21
Aplastic crisis caused by human parvovirus in two patients with hereditary stomatocytosis. 8
2171624 1990
22
A family of hereditary stomatocytosis associated with normal level of Na+-K+-ATPase activity of red blood cells. 8
6301265 1983
23
Missing band 7 membrane protein in two patients with high Na, low K erythrocytes. 8
7174793 1982
24
Role of the spleen in congenital stomatocytosis associated with high sodium-low potassium erythrocytes. 8
7230721 1981
25
Properties of the M antigen solubilized from genetically high potassium sheep red cells. 8
7219194 1981
26
Correction of the permeability defect in hereditary stomatocytosis by dimethyl adipimidate. 8
1264135 1976
27
Congenital stomatocytosis and chronic haemolytic anaemia. 8
128121 1975
28
Characteristics of the membrane defect in the hereditary stomatocytosis syndrome. 8
1148392 1975
29
Erythrocyte ion transport defects and hemolytic anemia: "hydrocytosis" and "desiccytosis". 8
5473420 1970
30
Congenital hemolytic anemia with high-sodium, low-potassium red cells. Studies of three generations of a family with a new variant. 8
4237839 1969
31
Congenital hemolytic anemia with high sodium, low potassium red cells. I. Studies of membrane permeability. 8
5637754 1968
32
Membrane raft actin deficiency and altered Ca2+-induced vesiculation in stomatin-deficient overhydrated hereditary stomatocytosis. 9 38
17961506 2008
33
Stomatocytosis of Standard Schnauzers is not associated with stomatin deficiency. 9 38
16168686 2007
34
Stomatin is mis-trafficked in the erythrocytes of overhydrated hereditary stomatocytosis, and is absent from normal primitive yolk sac-derived erythrocytes. 9 38
16197460 2005
35
Advances in understanding the pathogenesis of red cell membrane disorders. 38
31364155 2019
36
PIEZO1 Hypomorphic Variants in Congenital Lymphatic Dysplasia Cause Shape and Hydration Alterations of Red Blood Cells. 38
30930797 2019
37
SNPs altering ammonium transport activity of human Rhesus factors characterized by a yeast-based functional assay. 38
23967154 2013
38
Alterations of red blood cell metabolome in overhydrated hereditary stomatocytosis. 38
21859730 2011
39
A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis. 38
19644137 2009
40
[A case of hereditary over-hydrated stomatocytosis with stomatospherocytes and spherocytes in the blood]. 38
19837993 2009
41
The hereditary stomatocytoses: genetic disorders of the red cell membrane permeability to monovalent cations. 38
15071792 2004
42
Red blood cell membrane defects. 38
14692233 2003
43
Molecular basis of red cell membrane disorders. 38
12432217 2002
44
Model organisms: new insights into ion channel and transporter function. Stomatin homologues interact in Caenorhabditis elegans. 38
11287347 2001
45
Hereditary dehydrated and overhydrated stomatocytosis: recent advances. 38
10088641 1999

Variations for Overhydrated Hereditary Stomatocytosis

ClinVar genetic disease variations for Overhydrated Hereditary Stomatocytosis:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 RHAG NM_000324.2(RHAG): c.447T> G (p.Ile149Met) single nucleotide variant Pathogenic rs1554174425 6:49585826-49585826 6:49618113-49618113
2 RHAG NM_000324.2(RHAG): c.194T> C (p.Phe65Ser) single nucleotide variant Pathogenic rs863225468 6:49587039-49587039 6:49619326-49619326
3 RHAG NM_000324.2(RHAG): c.182T> G (p.Ile61Arg) single nucleotide variant Pathogenic rs863225469 6:49587051-49587051 6:49619338-49619338
4 RHAG NM_000324.2(RHAG): c.1007T> C (p.Leu336Ser) single nucleotide variant Uncertain significance rs1554172605 6:49578797-49578797 6:49611084-49611084

UniProtKB/Swiss-Prot genetic disease variations for Overhydrated Hereditary Stomatocytosis:

74
# Symbol AA change Variation ID SNP ID
1 RHAG p.Ile61Arg VAR_076283 rs863225469
2 RHAG p.Phe65Ser VAR_076284 rs863225468

Expression for Overhydrated Hereditary Stomatocytosis

Search GEO for disease gene expression data for Overhydrated Hereditary Stomatocytosis.

Pathways for Overhydrated Hereditary Stomatocytosis

GO Terms for Overhydrated Hereditary Stomatocytosis

Cellular components related to Overhydrated Hereditary Stomatocytosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 vesicle GO:0031982 8.62 STOM SRI

Biological processes related to Overhydrated Hereditary Stomatocytosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein homooligomerization GO:0051260 8.32 STOM

Sources for Overhydrated Hereditary Stomatocytosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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