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Disease Profile

Overhydrated hereditary stomatocytosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

D58.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Potassium sodium disorder of erythrocyte; Stomatocytosis I

Categories

Blood Diseases; Congenital and Genetic Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

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.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal mean corpuscular volume
0025065
Decreased mean corpuscular hemoglobin concentration
0025547
Hemolytic anemia
0001878
Increased red cell osmotic fragility
0005502
Reticulocytosis
Increased immature red blood cells
Increased number of immature red blood cells

[ more ]

0001923
Stomatocytosis
0004446
5%-29% of people have these symptoms
Abnormal thrombosis
Abnormal blood clot
0001977
Anisocytosis
Unequal size of red blood cells
0011273
Increased lactate dehydrogenase level
0025435
Intermittent jaundice
Intermittent yellow skin
Intermittent yellowing of skin

[ more ]

0001046
Splenomegaly
Increased spleen size
0001744
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Hepatomegaly
Enlarged liver
0002240
Hyperbilirubinemia
High blood bilirubin levels
0002904
Increased intracellular sodium
0003575
Jaundice
Yellow skin
Yellowing of the skin

[ more ]

0000952

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Overhydrated hereditary stomatocytosis. Click on the link to view a sample search on this topic.