Overhydrated Hereditary Stomatocytosis (OHST)

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Disease Ontology 12 DOID:0111562 OMIM 56 185000 KEGG 36 H01979 MeSH 43 D000745 ICD10 via Orphanet 33 D58.8

Orphanet 58 ORPHA3203 MedGen 41 C1861455 SNOMED-CT via HPO 68 16294009 165475005 18165001 26165005 263681008 46049004 57241006 61261009 80515008 more UMLS 71 C1861455

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 3203 Definition Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia . Epidemiology OHSt is very rare with only seven cases described in the literature so far. Clinical description Onset 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. Etiology In 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 methods Diagnosis 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 diagnosis The 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 counseling OHSt is transmitted as an autosomal dominant trait but de novo mutations are quite common. Management and treatment Treatment 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. Prognosis With 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 potassium sodium disorder of erythrocyte, is related to hereditary stomatocytosis 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 Glycosaminoglycan metabolism and heparan sulfate biosynthesis. Affiliated tissues include spleen, and related phenotypes are hemolytic anemia and reticulocytosis

Disease Ontology : ¹² A macrocytic anemia characterized by macrocytic hemolytic anemia and monovalent cation leak from red blood cells that has material basis in heterozygous mutation in RHAG on chromosome 6p12.3.

OMIM : ⁵⁶ 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 : ³⁶ 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 : ⁷³ 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.

Clinical features from OMIM:

185000

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