CHC
MCID: CRY019
MIFTS: 40

Cryohydrocytosis (CHC)

Categories: Blood diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Cryohydrocytosis

MalaCards integrated aliases for Cryohydrocytosis:

Name: Cryohydrocytosis 56 73 36 54
Stomatocytosis, Cold-Sensitive 56 73
Chc 56 73
Hereditary Cryohydrocytosis with Normal Stomatin 58
Anemia, Hemolytic, Congenital 43
Pseudohyperkalemia Cardiff 71

Characteristics:

Orphanet epidemiological data:

58
hereditary cryohydrocytosis with normal stomatin
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
patients are often misdiagnosed with spherocytosis
increased risk of post-splenectomy thrombotic complications


HPO:

31
cryohydrocytosis:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare haematological diseases


External Ids:

OMIM 56 185020
KEGG 36 H02002
MeSH 43 D000745
ICD10 via Orphanet 33 D58.8
Orphanet 58 ORPHA398088
MedGen 41 C1861453
UMLS 71 C1861453

Summaries for Cryohydrocytosis

OMIM : 56 Cryohydrocytosis is an exceedingly rare condition characterized by a mild stomatocytic hemolytic state with hyperbilirubinemia. A hallmark of this condition is that red blood cells (RBCs) lyse on storage at 4 degrees centigrade. RBC cation permeability is increased at 37 degrees centigrade, and the cells also accumulate sodium in the cold (summary by Coles et al., 1999). Patients present with fatigue, mild anemia, and pseudohyperkalemia due to a potassium leak from the RBCs (summary by Bogdanova et al., 2010). For a discussion of clinical and genetic heterogeneity of the hereditary stomatocytoses, see 194380. (185020)

MalaCards based summary : Cryohydrocytosis, also known as stomatocytosis, cold-sensitive, is related to hereditary stomatocytosis and hemolytic anemia. An important gene associated with Cryohydrocytosis is SLC4A1 (Solute Carrier Family 4 Member 1 (Diego Blood Group)), and among its related pathways/superpathways is Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds. The drugs Methotrexate and Tacrolimus have been mentioned in the context of this disorder. Affiliated tissues include liver, bone and bone marrow, and related phenotypes are splenomegaly and abnormality of metabolism/homeostasis

KEGG : 36 Cryohydrocytosis (CHC) is an exceedingly rare condition which shows a mild stomatocytic haemolytic state with hyperbilirubinaemia. Red blood cells from patients with CHC have increased membrane permeability to sodium and potassium ions, which is particularly pronounced at 0 degrees Celsius.

UniProtKB/Swiss-Prot : 73 Cryohydrocytosis: An autosomal dominant disorder of red cell membrane permeability characterized by cold-induced changes in cell volume, resulting in cold-sensitive stomatocytosis, and increased erythrocyte osmotic fragility and autohemolysis at 4 degrees Celsius. Patients present with mild to moderate hemolytic anemia, splenomegaly, fatigue, and pseudohyperkalemia due to a potassium leak from the erythrocytes.

Related Diseases for Cryohydrocytosis

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

(show all 47)
# Related Disease Score Top Affiliating Genes
1 hereditary stomatocytosis 29.7 STOM SLC4A1
2 hemolytic anemia 28.8 STOM SLC4A1 SLC2A1
3 stomatin-deficient cryohydrocytosis with neurologic defects 12.8
4 pseudohyperkalemia, familial, 2, due to red cell leak 11.8
5 congenital hemolytic anemia 11.6
6 overhydrated hereditary stomatocytosis 11.6
7 congenital nonspherocytic hemolytic anemia 11.5
8 pyruvate kinase deficiency of red cells 11.3
9 glut1 deficiency syndrome 1 11.2
10 hepatocellular carcinoma 10.4
11 liver disease 10.3
12 cataract 10.3
13 hepatitis c 10.3
14 pulmonary hypertension, primary, 3 10.2
15 cholangiocarcinoma 10.2
16 intrahepatic cholangiocarcinoma 10.2
17 liver cirrhosis 10.2
18 learning disability 10.2
19 elliptocytosis 2 10.2
20 elliptocytosis 3 10.2
21 hereditary spherocytosis 10.2
22 glucose transporter type 1 deficiency syndrome 10.2
23 hemochromatosis, type 1 10.0
24 pancreatic cancer 10.0
25 homocysteinemia 10.0
26 cervical cancer 10.0
27 body mass index quantitative trait locus 1 10.0
28 major affective disorder 8 10.0
29 major affective disorder 9 10.0
30 fatty liver disease, nonalcoholic 1 10.0
31 pulmonary hypertension, primary, 2 10.0
32 mulchandani-bhoj-conlin syndrome 10.0
33 opitz-gbbb syndrome 10.0
34 non-alcoholic fatty liver disease 10.0
35 non-alcoholic steatohepatitis 10.0
36 rabies 10.0
37 viral hepatitis 10.0
38 bilirubin metabolic disorder 10.0
39 lipid metabolism disorder 10.0
40 bipolar disorder 10.0
41 pancreatic adenocarcinoma 10.0
42 end stage renal failure 10.0
43 malignant hyperthermia 10.0
44 fatty liver disease 10.0
45 x-linked opitz g/bbb syndrome 10.0
46 48,xyyy 10.0
47 posttransplant acute limbic encephalitis 10.0

Graphical network of the top 20 diseases related to Cryohydrocytosis:



Diseases related to Cryohydrocytosis

Symptoms & Phenotypes for Cryohydrocytosis

Human phenotypes related to Cryohydrocytosis:

31
# Description HPO Frequency HPO Source Accession
1 splenomegaly 31 HP:0001744
2 abnormality of metabolism/homeostasis 31 HP:0001939
3 hemolytic anemia 31 HP:0001878
4 reticulocytosis 31 HP:0001923
5 stomatocytosis 31 HP:0004446

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Laboratory Abnormalities:
pseudohyperkalemia
increased autohemolysis and increased osmotic fragility at 5 degrees compared to 37 degrees c

Hematology:
increased reticulocyte count
hemolytic anemia, mild to moderate
stomatocytosis, cold-sensitive
macrospherocytosis on cold storage

Clinical features from OMIM:

185020

GenomeRNAi Phenotypes related to Cryohydrocytosis according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-113 9.44 SLC4A1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-115 9.44 SLC4A1
3 Increased shRNA abundance (Z-score > 2) GR00366-A-138 9.44 SLC2A1
4 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.44 SLC2A1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.44 SLC2A1
6 Increased shRNA abundance (Z-score > 2) GR00366-A-176 9.44 SLC2A1
7 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.44 SLC4A1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.44 SLC4A1
9 Increased shRNA abundance (Z-score > 2) GR00366-A-41 9.44 SLC2A1
10 Increased shRNA abundance (Z-score > 2) GR00366-A-43 9.44 SLC2A1
11 Increased shRNA abundance (Z-score > 2) GR00366-A-9 9.44 SLC2A1 SLC4A1
12 Increased shRNA abundance (Z-score > 2) GR00366-A-90 9.44 SLC2A1

Drugs & Therapeutics for Cryohydrocytosis

Drugs for Cryohydrocytosis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 37)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Methotrexate Approved Phase 2 1959-05-2, 59-05-2 126941
2
Tacrolimus Approved, Investigational Phase 2 104987-11-3 445643 439492 6473866
3
Busulfan Approved, Investigational Phase 2 55-98-1 2478
4
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
5
Sirolimus Approved, Investigational Phase 1, Phase 2 53123-88-9 5284616 6436030 46835353
6
Everolimus Approved Phase 1, Phase 2 159351-69-6 6442177 70789204
7
Miconazole Approved, Investigational, Vet_approved Phase 1, Phase 2 22916-47-8 4189
8
alemtuzumab Approved, Investigational Phase 1, Phase 2 216503-57-0
9
Ergocalciferol Approved, Nutraceutical Phase 2 50-14-6 5280793
10
Vitamin D Approved, Nutraceutical, Vet_approved Phase 2 1406-16-2
11
Vitamin D3 Approved, Nutraceutical Phase 2 67-97-0 6221 5280795
12
Calcium Approved, Nutraceutical Phase 2 7440-70-2 271
13 Thymoglobulin Phase 2
14 Antilymphocyte Serum Phase 2
15 Cyclosporins Phase 2
16 Calcineurin Inhibitors Phase 2
17 Immunosuppressive Agents Phase 1, Phase 2
18 Immunologic Factors Phase 1, Phase 2
19 Anti-Infective Agents Phase 1, Phase 2
20 Antibiotics, Antitubercular Phase 1, Phase 2
21 Antineoplastic Agents, Immunological Phase 1, Phase 2
22 Antifungal Agents Phase 1, Phase 2
23 Anti-Bacterial Agents Phase 1, Phase 2
24 Trace Elements Phase 2
25 Nutrients Phase 2
26 Vitamin D2 Phase 2
27 Ergocalciferols Phase 2
28 Micronutrients Phase 2
29 Vitamins Phase 2
30 Calcium, Dietary Phase 2
31 Calciferol Phase 2
32 Hormones Phase 2
33 Trientine Phase 2
34
Carbon monoxide Approved, Investigational Phase 1 630-08-0 281
35 Neurotransmitter Agents Phase 1
36 Antimetabolites Phase 1
37 pyruvate

Interventional clinical trials:

(show all 12)
# Name Status NCT ID Phase Drugs
1 An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies Recruiting NCT03853798 Phase 3 AG-348
2 An Open-Label Study To Evaluate the Efficacy and Safety of AG-348 in Regularly Transfused Adult Subjects With Pyruvate Kinase (PK) Deficiency Recruiting NCT03559699 Phase 3 AG-348
3 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Subjects With Pyruvate Kinase Deficiency Recruiting NCT03548220 Phase 3 AG-348;Placebo
4 A Phase II Study of Hematopoietic Stem Cell Therapy for Young Adults With Severe Sickle Cell Disease Completed NCT01565616 Phase 2 Conditioning Regimen with Bone Marrow Transplant
5 Nonmyeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation For Severe Congenital Anemias Including Sickle Cell Disease (SCD) and Beta-Thalassemia Recruiting NCT00061568 Phase 1, Phase 2 Alemtuzumab;Sirolimus
6 A Phase 2, Open Label, Randomized, Dose Ranging, Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of AG-348 in Adult Patients With Pyruvate Kinase Deficiency Active, not recruiting NCT02476916 Phase 2 AG-348
7 Daily Vitamin D for Sickle-cell Respiratory Complications Not yet recruiting NCT04170348 Phase 2 Daily oral vitamin D3, 3,333 IU;Bolus oral vitamin D3, 100,000 IU;Placebo oral tablet
8 Gene Therapy for Pyruvate Kinase Deficiency (PKD): A Phase I Clinical Trial to Evaluate the Safety of the Infusion of Autologous CD34+ Cells Transduced With a Lentiviral Vector Carrying the Codon Optimized Red Cell Pyruvate Kinase (coRPK) Gene in Adult and Pediatric Subjects With PKD Recruiting NCT04105166 Phase 1
9 A Phase 1 Open Labeled Single Ascending Dose Followed by Multiple Ascending Dose Safety and Pharmacokinetic Study of HBI-002 Carbon Monoxide Oral Liquid Drug Product in Healthy Adult Volunteers. Not yet recruiting NCT03926819 Phase 1 HBI-002
10 Pyruvate Kinase Deficiency Global Longitudinal Registry Recruiting NCT03481738
11 Pyruvate Kinase Deficiency (PKD) Natural History Study Active, not recruiting NCT02053480
12 Pyruvate Kinase Deficiency Epidemiological Study. An International, Multicentre, Epidemiological Observational Study Not yet recruiting NCT03866590

Search NIH Clinical Center for Cryohydrocytosis

Cochrane evidence based reviews: anemia, hemolytic, congenital

Genetic Tests for Cryohydrocytosis

Anatomical Context for Cryohydrocytosis

MalaCards organs/tissues related to Cryohydrocytosis:

40
Liver, Bone, Bone Marrow, Testes

Publications for Cryohydrocytosis

Articles related to Cryohydrocytosis:

(show all 25)
# Title Authors PMID Year
1
Two further British families with the 'cryohydrocytosis' form of hereditary stomatocytosis. 61 56 6
11442486 2001
2
Two British families with variants of the 'cryohydrocytosis' form of hereditary stomatocytosis. 61 56 6
10554820 1999
3
Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1. 56 6
16227998 2005
4
Four pedigrees of the cation-leaky hereditary stomatocytosis class presenting with pseudohyperkalaemia. Novel profile of temperature dependence of Na+-K+ leak in a xerocytic form. 56 6
15142123 2004
5
A variant of hereditary stomatocytosis with marked pseudohyperkalaemia. 56 6
10050708 1999
6
Pseudohyperkalaemia associated with hereditary spherocytosis in four members of a family. 56 6
7831176 1994
7
Cryohydrocytosis: increased activity of cation carriers in red cells from a patient with a band 3 mutation. 61 56
20015879 2010
8
A second locus mapping to 2q35-36 for familial pseudohyperkalaemia. 56
15470366 2004
9
A race to the lab. 56
11897285 2002
10
A NEW CONGENITAL HEMOLYTIC ANEMIA WITH DEFORMED ERYTHROCYTES ("STOMATOCYTES") AND REMARKABLE SUSCEPTIBILITY OF ERYTHROCYTES TO COLD HEMOLYSIS IN VITRO. I. CLINICAL AND HEMATOLOGIC STUDIES. 56
14296416 1965
11
Four new cases of stomatin-deficient hereditary stomatocytosis syndrome: association of the stomatin-deficient cryohydrocytosis variant with neurological dysfunction. 54 61
15180870 2004
12
Advances in understanding the pathogenesis of red cell membrane disorders. 61
31364155 2019
13
The Molecular Basis for Altered Cation Permeability in Hereditary Stomatocytic Human Red Blood Cells. 61
29713289 2018
14
Pulmonary endarterectomy is effective and safe in patients with haemoglobinopathies and abnormal red blood cells: the Papworth experience. 61
26987879 2016
15
Glucide metabolism disorders (excluding glycogen myopathies). 61
23622389 2013
16
Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome. 61
21791420 2011
17
South-east Asian ovalocytosis and the cryohydrocytosis form of hereditary stomatocytosis show virtually indistinguishable cation permeability defects. 61
21255002 2011
18
A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis. 61
19644137 2009
19
Hereditary stomatocytosis and cation-leaky red cells--recent developments. 61
19261491 2009
20
The hereditary stomatocytoses: genetic disorders of the red cell membrane permeability to monovalent cations. 61
15071792 2004
21
Cold storage of 'cryohydrocytosis' red cells: the osmotic susceptibility of the cold-stored erythrocyte. 61
12930402 2003
22
Familial pseudohyperkalaemia Cardiff: a mild version of cryohydrocytosis. 61
11918557 2002
23
Rapid flow cytometric test for the diagnosis of membrane cytoskeleton-associated haemolytic anaemia. 61
11122157 2000
24
Temperature effects on cation transport in hereditary stomatocytosis and allied disorders. 61
10607015 1999
25
Missing band 7 membrane protein in two patients with high Na, low K erythrocytes. 61
7174793 1982

Variations for Cryohydrocytosis

ClinVar genetic disease variations for Cryohydrocytosis:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SLC4A1 NM_000342.4(SLC4A1):c.2191T>C (p.Ser731Pro)SNV Pathogenic 218182 rs863225461 17:42330606-42330606 17:44253238-44253238
2 SLC4A1 NM_000342.4(SLC4A1):c.2201A>G (p.His734Arg)SNV Pathogenic 218183 rs863225462 17:42330596-42330596 17:44253228-44253228
3 SLC4A1 NM_000342.4(SLC4A1):c.2060T>C (p.Leu687Pro)SNV Pathogenic 218184 rs863225463 17:42330737-42330737 17:44253369-44253369
4 SLC4A1 NM_000342.4(SLC4A1):c.1765C>T (p.Arg589Cys)SNV Pathogenic 17764 rs121912745 17:42333076-42333076 17:44255708-44255708
5 SLC4A1 NM_000342.3(SLC4A1):c.118G>A (p.Glu40Lys)SNV Conflicting interpretations of pathogenicity 17756 rs45562031 17:42338993-42338993 17:44261625-44261625

UniProtKB/Swiss-Prot genetic disease variations for Cryohydrocytosis:

73
# Symbol AA change Variation ID SNP ID
1 SLC4A1 p.Leu687Pro VAR_039293 rs863225463
2 SLC4A1 p.Ser731Pro VAR_039295 rs863225461
3 SLC4A1 p.His734Arg VAR_039296 rs863225462

Expression for Cryohydrocytosis

Search GEO for disease gene expression data for Cryohydrocytosis.

GO Terms for Cryohydrocytosis

Cellular components related to Cryohydrocytosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular exosome GO:0070062 9.61 STOM SLC4A1 SLC2A1
2 integral component of plasma membrane GO:0005887 9.5 STOM SLC4A1 SLC2A1
3 membrane raft GO:0045121 9.4 STOM SLC2A1
4 basolateral plasma membrane GO:0016323 9.37 SLC4A1 SLC2A1
5 vesicle GO:0031982 9.26 STOM SLC2A1
6 Z disc GO:0030018 9.16 SLC4A1 SLC2A1
7 melanosome GO:0042470 8.96 STOM SLC2A1
8 blood microparticle GO:0072562 8.8 STOM SLC4A1 SLC2A1

Sources for Cryohydrocytosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....