overhydrated hereditary stomatocytosis

Overhydrated Hereditary Stomatocytosis (OHSt): A Rare Disorder

Overhydrated hereditary stomatocytosis (OHSt) is a rare disorder characterized by abnormalities in erythrocytic volume homeostasis [6]. It is a type of hemolytic anemia, which means that the red blood cells are destroyed faster than they can be made, leading to a decrease in the number of healthy red blood cells in the body.

Clinical Features

The clinical features of OHSt include:

• Hemolytic Anemia: A condition where the red blood cells are destroyed faster than they can be made [4].
• Splenomegaly: Enlargement of the spleen, which can lead to a range of complications [9].
• Gallstones: The formation of stones in the gallbladder, which can cause pain and other symptoms [9].
• Jaundice: A yellowing of the skin and eyes due to high levels of bilirubin in the blood [9].

Causes

OHSt is caused by a defect in the red cell membrane permeability to monovalent cations, leading to an increase in sodium and potassium ions entering the cell. This results in an increase in cellular water content, producing large, osmotically fragile cells that are prone to destruction [10].

Genetic Link

OHSt is frequently linked to mutations in genes that encode components of the band 3 complex, such as RHAG [11]. The altered band 3 protein complex mediates the cation leaks that are characteristic of OHSt.

Age of Onset

The onset of OHSt typically occurs during the neonatal period or infancy, with hemolytic anemia requiring occasional blood transfusions [12].

Overall, overhydrated hereditary stomatocytosis is a rare and complex disorder that requires careful management to prevent complications.

Clinical Presentation of Overhydrated Hereditary Stomatocytosis

Overhydrated hereditary stomatocytosis (OHSt) is a disorder characterized by hemolytic anemia, which can manifest in various ways. The clinical presentation of OHSt typically includes:

• Hemolytic Anemia: A decrease in the number of red blood cells or their ability to carry oxygen, leading to fatigue, weakness, and shortness of breath [1] [3].
• Fatigue and Pallor: Patients may experience fatigue and pallor due to inadequate oxygen delivery to tissues [1] [3].
• Jaundice: Yellowing of the skin and eyes (jaundice) can occur as a result of hemolysis [1] [3].
• Splenomegaly: Enlargement of the spleen, which can be painful and tender to touch [9].
• Gallstone Formation: Prolonged hemolysis can lead to the formation of gallstones [9].

In some cases, OHSt may present with additional symptoms, such as:

• Exercise-Induced Episodes: Patients may experience episodes of more severe anemia triggered by physical activity [4] [5].
• Temperature-Dependent Red Cell Cation Leak: The red cell cation leak can be temperature-dependent, which may contribute to the variability in clinical presentation [5].

It's essential to note that the severity and presentation of OHSt can vary widely among individuals. Some patients may experience mild anemia or no symptoms at all, while others may have more severe manifestations [6] [7].

Overhydrated hereditary stomatocytosis (OHSt) can be diagnosed through a combination of clinical evaluation, laboratory tests, and genetic analysis.

Laboratory Findings

• Hemoglobinuria
• Reticulocytosis
• Increased red cell hemolysis by shear stress
• Increased mean corpuscular volume (MCV)
• Increased mean corpuscular hemoglobin concentration (MCHC)

These findings can be observed in the peripheral blood smear, CBC count, and reticulocyte count.

Diagnostic Tests

• Peripheral blood smear: This test can show macrocytosis with stomatocytosis (up to 50% of red blood cells), which also demonstrate a decreased MCHC [9].
• CBC count: This test can reveal anemia, which is a hallmark of OHSt.
• Reticulocyte count: This test can show increased reticulocytes, indicating active bone marrow response to hemolysis.
• Osmotic fragility tests: These tests can help diagnose OHSt by showing decreased osmotic resistance of red blood cells [15].
• Miscellaneous tests:
  • Coombs test (direct/indirect): Negative results rule out autoimmune hemolytic anemia [8].
  • Screening of abnormal forms of hemoglobin and erythrocyte osmotic fragility test: These tests can help differentiate OHSt from other hemolytic anemias.

Genetic Analysis

• Genetic testing can identify heterozygous mutations in the RHAG gene, confirming the diagnosis of OHSt [2].
• The most severe form of OHSt is caused by heterozygous missense mutations in RHAG, which alter amino acids lining the putative transport channel, making it permeable to Na+ ions [10].

Diagnostic Teams

A diagnostic team for OHSt may include:

• Genetics
• Hematology

These teams can help coordinate providers and order diagnostic tests as needed.

References: [2] - Genetic testing identified a heterozygous mutation in the RHAG gene, confirming the diagnosis of OHSt. [8] - Coombs test (direct/indirect) resulted negative, as well as screening of abnormal forms of hemoglobin and erythrocyte osmotic fragility test. [9] - The peripheral smear demonstrates macrocytosis with stomatocytosis (up to 50% of red blood cells), which also demonstrate a decreased MCHC. [10] - The most severe form of overhydrated hereditary stomatocytosis is caused by heterozygous missense mutations in RHAG, the gene coding for the band 3 protein. [15] - Osmotic fragility tests can help diagnose OHSt by showing decreased osmotic resistance of red blood cells.

Treatment Overview

Overhydrated hereditary stomatocytosis (OHSt) is a rare disorder characterized by abnormalities in erythrocytic volume homeostasis, leading to hemolytic anemia. While there is no specific treatment for the underlying condition, various management strategies can help alleviate symptoms and prevent complications.

Blood Transfusions

In cases of severe anemia, blood transfusions may be necessary to maintain adequate red blood cell count and prevent tissue hypoxia [1]. However, this approach should be used judiciously, as repeated transfusions can lead to iron overload and other complications [9].

Folic Acid Supplementation

Folic acid supplementation is recommended in patients with anemia due to OHSt. This treatment helps maintain normal red blood cell production and prevent megaloblastic anemia [4]. Folic acid (Folvite) is the only medication used to treat stomatocytosis syndromes, including OHSt.

Iron Chelating Therapy

In rare cases with severe anemia, iron chelating therapy may be necessary to manage iron overload and prevent complications such as liver damage [11].

Phototherapy

Newborns with OHSt may require phototherapy due to immature glucuronyl transferase activity. This treatment helps reduce bilirubin levels and prevent kernicterus.

Splenectomy Contraindication

Splenectomy is contraindicated in patients with OHSt, as it can lead to unpredictable outcomes and increased risk of complications [2, 14].

Monitoring and Management

Regular monitoring for cholelithiasis (gallstones) and iron overload is essential in patients with OHSt. Treatment is mainly symptomatic, and management strategies should be tailored to individual patient needs.

References:

[1] May 21, 2024 — Patients with hereditary stomatocytosis syndromes do not require splenectomy. [2] May 21, 2024 — The results of splenectomy vary, and the benefits are unpredictable. [3] Hereditary stomatocytoses. Overhydrated hereditary stomatocytosis is an autosomal dominant disorder characterised by the presence of large numbers of stomatocytes on blood smears in association with moderately severe to severe anaemia [4] Overhydrated hereditary stomatocytosis (OHS) ... Treatment with phototherapy could be required in neonatal period, due to immature glucuronyl transferase activity in the newborns. [9] Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia. ... Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [11] Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia. ... Treatment involves blood transfusions, when necessary, together with management of biliary lithiasis and iron overload. [14] Overhydrated hereditary stomatocytosis (OHSt) is a disorder of red cell membrane permeability to monovalent cations and is characterized clinically by hemolytic anemia. ... Treatment involves blood transfusions, when necessary, together with management of biliary lithiasis and iron overload.

Differential Diagnosis of Overhydrated Hereditary Stomatocytosis

Overhydrated hereditary stomatocytosis (OHSt) is a rare disorder characterized by abnormalities in erythrocytic volume homeostasis. When diagnosing OHSt, it's essential to consider other potential causes of hemolysis and anemia. Here are some differential diagnoses to consider:

• Hereditary Spherocytosis: This is another form of hereditary stomatocytosis that can present with similar clinical features as OHSt.
• Hemoglobinopathy or Red Cell Enzyme Defects: Conditions such as thalassemia, glutathione peroxidase deficiency, and glucose-6-phosphate dehydrogenase (G6PD) deficiency can also cause hemolysis and anemia.
• Dehydrated Hereditary Stomatocytosis: This is a rare disorder that can present with similar clinical features as OHSt, but it's characterized by dehydration of red blood cells rather than overhydration.
• Other Causes of Hemolysis: Other conditions such as autoimmune hemolytic anemia, microangiopathic hemolytic anemia, and paroxysmal nocturnal hemoglobinuria (PNH) can also cause hemolysis and anemia.

Key Points to Consider

• The visual aspect of red blood cells varies depending on the variant: very stomatocytic for OHSt, xerocytic for dehydrated hereditary stomatocytosis.
• Moderate-to-severe lifelong hemolytic anemia is most commonly associated with OHSt [9].
• Differential diagnoses include other causes of hemolysis, including hereditary spherocytosis, overhydrated hereditary stomatocytosis, hemoglobinopathy or red cell enzyme defects [4].

References

[1] The differential diagnosis should include the most common form of hereditary stomatocytosis, dehydrated hereditary stomatocytosis, as well as hereditary ... (context 1) [2] Overhydrated hereditary stomatocytosis (OHSt) is a rare disorder characterized by abnormalities in erythrocytic volume homeostasis. (context 2) [3] Differential diagnoses include other causes of hemolysis, including hereditary spherocytosis, overhydrated hereditary stomatocytosis, hemoglobinopathy or red ... (context 4) [9] May 21, 2024 — Overhydrated hereditary stomatocytosis (OHSt)​​ The degree of hemolysis and anemia varies. Moderate-to-severe lifelong hemolytic anemia is most ... (context 9)