MCID: DHY016
MIFTS: 32

Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema

Categories: Genetic diseases, Rare diseases

Aliases & Classifications for Dehydrated Hereditary Stomatocytosis 1 with or Without...

MalaCards integrated aliases for Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema:

Name: Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema 57 75
Dehydrated Hereditary Stomatocytosis 57 53 75 37 13
Pseudohyperkalemia Edinburgh 57 75
Xerocytosis, Hereditary 57 76
Hereditary Xerocytosis 53 75
Pshk1 57 75
Dhs1 57 75
Dhs 57 75
Dehydrated Hereditary Stomatocytosis with or Without Pseudohyperkalemia and/or Perinatal Edema 57
Stomatocytosis, Dehydrated, Hereditary, with/without Pseudohyperkalemia and/or Perinatal Edema 40
Pseudohyperkalemia, Familial, 1, Due to Red Cell Leak; Pshk1 57
Pseudohyperkalemia, Familial, 1, Due to Red Cell Leak 57
Familial Pseudohyperkalemia 1 Due to Red Cell Leak 75
Dehydrated Hereditary Stomatocytosis; Dhs 57
Desiccytosis, Hereditary 57
Desiccytosis Hereditary 53
Hereditary Desiccytosis 75
Xerocytosis Hereditary 53
Xerocytosis 73

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
splenectomy increases thrombotic risk in these patients
episodes of fatigue or weakness (in some patients)
hemolysis may be exercise-induced


HPO:

32
dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Dehydrated Hereditary Stomatocytosis 1 with or Without...

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 3202Disease definitionDehydrated hereditary stomatocytosis (DHS) is a rare hemolytic anemia characterized by a decreased red cell osmotic fragility due to a defect in cation permeability, resulting in red cell dehydration and mild to moderate compensated hemolysis. Pseudohyperkalemia (loss of potassium ions from red cells on storage at room temperature) is sometimes observed.EpidemiologyThe prevalence of DHS is unknown but to date, about 20 families with DHS have been described in the literature.Clinical descriptionThe clinical presentation of the disease is very heterogeneous. Onset of DHS may occur during the perinatal period with occurrence of edema and ascites (most often not related to an underlying anemia) that usually resolve spontaneously during the first weeks of life but may rarely lead to hydrops fetalis (see this term). Most adult patients present a mild anemia or a totally compensated hemolysis, with fatigue, icterus, splenomegaly and risks of secondary complications including cholelithiasis. Patients can also be referred for unexplained hemochromatosis, since iron overload is frequently associated with the disease. Thrombotic complications (arterial and venous events, including portal vein thrombosis (see this term) and pulmonary hypertension) have been described at a high rate after splenectomy.EtiologyMost reported DHS cases are caused by gain-of-function mutations in the genePIEZO1 (16q24.3) which encodes part of a mechanosensitive ion channel. This results in increased red cell membrane permeability for cations that consequently leads to cation depletion, dehydration and shortened red cell survival. Rare atypical forms have been associated with mutations in SLC4A1 (17q21.31), coding for the Band 3 anion transport protein, or KCNN4 (19q13.2) which codes for the putative Gardos channel.Diagnostic methodsDiagnosis relies on laboratory findings. The typical presentation includes normal hemoglobin level or mild anemia, normal mean cell volume (MCV) or mild macrocytosis, normal or elevated mean corpuscular hemoglobin concentration (MCHC), elevated reticulocytosis, and a small number of stomatocytes (in vitro leakage and is clinically irrelevant. Measurement of ferritin level and liver magnetic resonance imaging (MRI) are performed to evaluate iron overload. Genetic screening of the causative genes can be performed after phenotypic investigations.Differential diagnosisDifferential diagnoses include other causes of hemolysis, including hereditary spherocytosis, overhydrated hereditary stomatocytosis, hemoglobinopathy or red cell enzyme deficiencies such as hemolytic anemia due to red cell pyruvate kinase deficiency (see these terms).Genetic counselingTransmission is autosomal dominant and genetic counseling should be offered to affected families.Management and treatmentTreatment is mainly symptomatic. Occurrence of cholelithiasis should be regularly monitored. Folic acid supplementation should be proposed in case of anemia. Pregnancy should be closely monitored. Iron status should be regularly monitored by serum ferritinemia and liver MRI. Iron depletion, most often by phlebotomy, is proposed when ferritinemia reaches the threshold of 1000 ng/ml or when iron liver overload is present. Splenectomy is contraindicated in DHS due to an elevated risk of life threatening arterial and venous thrombotic events.PrognosisOverall prognosis is favorable in well managed patients (not splenectomized and with regular monitoring of their iron status). Splenectomized patients are at risk of early or late thrombotic events.Visit the Orphanet disease page for more resources.

MalaCards based summary : Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema, also known as dehydrated hereditary stomatocytosis, is related to dermatitis herpetiformis and dermatitis herpetiformis, familial. An important gene associated with Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema is PIEZO1 (Piezo Type Mechanosensitive Ion Channel Component 1). Affiliated tissues include spleen, liver and heart, and related phenotypes are jaundice and pallor

OMIM : 57 Dehydrated hereditary stomatocytosis (DHS), also known as hereditary xerocytosis, is an autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. DHS erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. DHS patients typically exhibit mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration (summary by Zarychanski et al., 2012). Patients may also show perinatal edema and pseudohyperkalemia due to loss of K+ from red cells stored at room temperature. A minor proportion of red cells appear as stomatocytes on blood films. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. The course of DHS is frequently associated with iron overload, which may lead to hepatosiderosis (summary by Albuisson et al., 2013). The 'leaky red blood cells' in familial pseudohyperkalemia show a temperature-dependent loss of potassium when stored at room temperature, manifesting as apparent hyperkalemia. The red blood cells show a reduced life span in vivo, but there is no frank hemolysis. Studies of cation content and transport show a marginal increase in permeability at 37 degrees C and a degree of cellular dehydration, qualitatively similar to the changes seen in dehydrated hereditary stomatocytosis. Physiologic studies show that the passive leak of potassium has an abnormal temperature dependence, such that the leak is less sensitive to temperature than that in normal cells (summary by Iolascon et al., 1999). Carella et al. (2004) noted that 3 clinical forms of pseudohyperkalemia unassociated with hematologic manifestations, based predominantly on the leak-temperature dependence curve, had been reported: (1) pseudohyperkalemia Edinburgh, in which the curve has a shallow slope; (2) pseudohyperkalemia Chiswick or Falkirk (see 609153), in which the curve is shouldered; and (3) pseudohyperkalemia Cardiff (see 609153), in which the temperature dependence of the leak shows a 'U-shaped' profile with a minimum at 23 degrees C. Gore et al. (2004) stated that potassium-flux temperature profiles are consistent both from year to year in an individual as well as consistent within affected members of a pedigree. (194380)

UniProtKB/Swiss-Prot : 75 Dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema: An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. DHS erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. DHS patients typically exhibit mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Patients may also show perinatal edema and pseudohyperkalemia due to loss of potassium from red cells stored at room temperature. A minor proportion of red cells appear as stomatocytes on blood films. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. The course of DHS is frequently associated with iron overload, which may lead to hepatosiderosis.

Related Diseases for Dehydrated Hereditary Stomatocytosis 1 with or Without...

Diseases related to Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 dermatitis herpetiformis 11.8
2 dermatitis herpetiformis, familial 11.2
3 dehydrated hereditary stomatocytosis 2 11.0

Symptoms & Phenotypes for Dehydrated Hereditary Stomatocytosis 1 with or Without...

Symptoms via clinical synopsis from OMIM:

57
Hematology:
increased reticulocyte count
anemia, chronic hemolytic
macrocytosis (in some patients)
increased mean corpuscular hemoglobin concentration
stomatocytes (may be few in number)
more
Cardiovascular Heart:
pericardial effusion, perinatal (rare)

Respiratory Lung:
pleural effusion, perinatal (rare)

Abdomen Liver:
hepatomegaly (in some patients)
hepatosiderosis (rare)
hepatitis (rare)

AbdomenSpleen:
splenomegaly (in some patients)

Skin Nails Hair Skin:
jaundice, intermittent (in some patients)
pallor (in some patients)
edema, generalized perinatal (in some patients)

Head And Neck Eyes:
scleral icterus (in some patients)

Cardiovascular Vascular:
thrombosis, susceptibility to (post-splenectomy patients)

Abdomen:
ascites, perinatal (in some patients)

Abdomen Biliary Tract:
cholelithiasis (in some patients)

Genitourinary Kidneys:
hemoglobinuria (in some patients)

Laboratory Abnormalities:
pseudohyperkalemia, due to ex vivo efflux of potassium from red cells (in some patients)
increased serum bilirubin (in some patients)
decreased serum haptoglobin (in some patients)
increased serum ferritin (in some patients)
iron overload (in some patients)


Clinical features from OMIM:

194380

Human phenotypes related to Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 jaundice 32 occasional (7.5%) HP:0000952
2 pallor 32 occasional (7.5%) HP:0000980
3 cholelithiasis 32 occasional (7.5%) HP:0001081
4 splenomegaly 32 occasional (7.5%) HP:0001744
5 reticulocytosis 32 HP:0001923
6 hepatomegaly 32 occasional (7.5%) HP:0002240
7 increased serum ferritin 32 occasional (7.5%) HP:0003281
8 hemoglobinuria 32 occasional (7.5%) HP:0003641
9 exercise-induced hemolysis 32 HP:0005535
10 increased red cell hemolysis by shear stress 32 HP:0008269
11 hepatitis 32 occasional (7.5%) HP:0012115

Drugs & Therapeutics for Dehydrated Hereditary Stomatocytosis 1 with or Without...

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Dallas Heart Study 2: Return Clinic Visit for the Dallas Heart Study Cohort Completed NCT00344903

Search NIH Clinical Center for Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema

Genetic Tests for Dehydrated Hereditary Stomatocytosis 1 with or Without...

Anatomical Context for Dehydrated Hereditary Stomatocytosis 1 with or Without...

MalaCards organs/tissues related to Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema:

41
Spleen, Liver, Heart, Lung

Publications for Dehydrated Hereditary Stomatocytosis 1 with or Without...

Articles related to Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema:

(show all 23)
# Title Authors Year
1
Dehydrated Hereditary Stomatocytosis Presenting as Severe Perinatal Ascites and Cholestasis. ( 29952828 )
2018
2
Dehydrated hereditary stomatocytosis masquerading as MDS. ( 25927085 )
2015
3
Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis). ( 26178367 )
2015
4
Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. ( 23479567 )
2013
5
Slower Piezo1 inactivation in dehydrated hereditary stomatocytosis (xerocytosis). ( 23972832 )
2013
6
Dehydrated hereditary stomatocytosis and recurrent prenatal ascites. ( 23815216 )
2013
7
Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. ( 23695678 )
2013
8
First-trimester nuchal abnormalities secondary to dehydrated hereditary stomatocytosis. ( 19655317 )
2009
9
Antiphospholipid antibodies in a family with dehydrated hereditary stomatocytosis. ( 18377960 )
2008
10
Dehydrated hereditary stomatocytosis mimicking familial hyperkalaemic hypertension: clinical and genetic investigation. ( 17253968 )
2007
11
Mild dehydrated hereditary stomatocytosis revealed by marked hepatosiderosis. ( 16898969 )
2006
12
Dehydrated hereditary stomatocytosis is associated with neonatal hepatitis. ( 15238150 )
2004
13
Dehydrated hereditary stomatocytosis with transient perinatal ascites. ( 12937055 )
2003
14
An extreme consequence of splenectomy in dehydrated hereditary stomatocytosis: gradual thrombo-embolic pulmonary hypertension and lung-heart transplantation. ( 12908798 )
2003
15
Sub-lethal hydrops as a manifestation of dehydrated hereditary stomatocytosis in two consecutive pregnancies. ( 12749034 )
2003
16
Dehydrated hereditary stomatocytosis: a cause of prenatal ascites. ( 11787034 )
2001
17
Pleiotropic syndrome of dehydrated hereditary stomatocytosis, pseudohyperkalemia, and perinatal edema maps to 16q23-q24. ( 11001917 )
2000
18
Dehydrated hereditary stomatocytosis is not linked to the hlK1 locus, a Gardos channel candidate, on chromosome 19q13.2. ( 10189206 )
1999
19
Exclusion of the stomatin, alpha-adducin and beta-adducin loci in a large kindred with dehydrated hereditary stomatocytosis. ( 9883810 )
1999
20
Familial pseudohyperkalemia maps to the same locus as dehydrated hereditary stomatocytosis (hereditary xerocytosis). ( 10216110 )
1999
21
A genetic syndrome associating dehydrated hereditary stomatocytosis, pseudohyperkalaemia and perinatal oedema. ( 9827909 )
1998
22
Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): mapping of locus to chromosome 16 (16q23-qter). ( 9718354 )
1998
23
Dehydrated hereditary stomatocytosis--a report of two families and a review of the literature. ( 6462777 )
1984

Variations for Dehydrated Hereditary Stomatocytosis 1 with or Without...

UniProtKB/Swiss-Prot genetic disease variations for Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema:

75 (show all 12)
# Symbol AA change Variation ID SNP ID
1 PIEZO1 p.Gly718Ser VAR_069822 rs755885744
2 PIEZO1 p.Gly782Ser VAR_069823 rs200970763
3 PIEZO1 p.Arg808Gln VAR_069824 rs202103485
4 PIEZO1 p.Ser1117Leu VAR_069825 rs587777765
5 PIEZO1 p.Arg1358Pro VAR_069826 rs587776990
6 PIEZO1 p.Ala2003Asp VAR_069827
7 PIEZO1 p.Ala2020Thr VAR_069828 rs587776989
8 PIEZO1 p.Ala2020Val VAR_069829 rs587777764
9 PIEZO1 p.Thr2127Met VAR_069830 rs587776991
10 PIEZO1 p.Met2225Arg VAR_069832 rs587776987
11 PIEZO1 p.Arg2456His VAR_069833 rs587776988
12 PIEZO1 p.Arg2488Gln VAR_069834 rs749288233

ClinVar genetic disease variations for Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema:

6
(show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 PIEZO1 NM_001142864.3(PIEZO1): c.6674T> G (p.Met2225Arg) single nucleotide variant Pathogenic rs587776987 GRCh37 Chromosome 16, 88783293: 88783293
2 PIEZO1 NM_001142864.3(PIEZO1): c.6674T> G (p.Met2225Arg) single nucleotide variant Pathogenic rs587776987 GRCh38 Chromosome 16, 88716885: 88716885
3 PIEZO1 NM_001142864.3(PIEZO1): c.7367G> A (p.Arg2456His) single nucleotide variant Pathogenic rs587776988 GRCh37 Chromosome 16, 88782212: 88782212
4 PIEZO1 NM_001142864.3(PIEZO1): c.7367G> A (p.Arg2456His) single nucleotide variant Pathogenic rs587776988 GRCh38 Chromosome 16, 88715804: 88715804
5 PIEZO1 NM_001142864.3(PIEZO1): c.6058G> A (p.Ala2020Thr) single nucleotide variant Pathogenic rs587776989 GRCh37 Chromosome 16, 88786583: 88786583
6 PIEZO1 NM_001142864.3(PIEZO1): c.6058G> A (p.Ala2020Thr) single nucleotide variant Pathogenic rs587776989 GRCh38 Chromosome 16, 88720175: 88720175
7 PIEZO1 NM_001142864.3(PIEZO1): c.4073G> C (p.Arg1358Pro) single nucleotide variant Pathogenic rs587776990 GRCh37 Chromosome 16, 88791913: 88791913
8 PIEZO1 NM_001142864.3(PIEZO1): c.4073G> C (p.Arg1358Pro) single nucleotide variant Pathogenic rs587776990 GRCh38 Chromosome 16, 88725505: 88725505
9 PIEZO1 NM_001142864.3(PIEZO1): c.6380C> T (p.Thr2127Met) single nucleotide variant Pathogenic rs587776991 GRCh37 Chromosome 16, 88786073: 88786073
10 PIEZO1 NM_001142864.3(PIEZO1): c.6380C> T (p.Thr2127Met) single nucleotide variant Pathogenic rs587776991 GRCh38 Chromosome 16, 88719665: 88719665
11 PIEZO1 NM_001142864.3(PIEZO1): c.7483_7488dupCTGGAG (p.Glu2496_Glu2497insLeuGlu) duplication Pathogenic rs587776992 GRCh37 Chromosome 16, 88782091: 88782096
12 PIEZO1 NM_001142864.3(PIEZO1): c.7483_7488dupCTGGAG (p.Glu2496_Glu2497insLeuGlu) duplication Pathogenic rs587776992 GRCh38 Chromosome 16, 88715683: 88715688

Expression for Dehydrated Hereditary Stomatocytosis 1 with or Without...

Search GEO for disease gene expression data for Dehydrated Hereditary Stomatocytosis 1 with or Without Pseudohyperkalemia and/or Perinatal Edema.

Pathways for Dehydrated Hereditary Stomatocytosis 1 with or Without...

GO Terms for Dehydrated Hereditary Stomatocytosis 1 with or Without...

Sources for Dehydrated Hereditary Stomatocytosis 1 with or Without...

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