dehydrated hereditary stomatocytosis

Dehydrated Hereditary Stomatocytosis (DHS): A Rare Hemolytic Anemia

Dehydrated 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 [1]. This condition is also known as hereditary xerocytosis.

Key Features:

• Red Cell Dehydration: The primary feature of DHS is the dehydration of red blood cells, which leads to a decrease in their osmotic fragility [2].
• Mild to Moderate Compensated Hemolysis: Despite the red cell dehydration, the body's compensatory mechanisms help to maintain a stable level of hemoglobin and prevent severe anemia [3].
• Pseudohyperkalemia: In some cases, DHS can lead to pseudohyperkalemia, where potassium ions are lost from red cells on storage at room temperature [4].

Genetic Basis:

DHS is caused by heterozygous or homozygous mutations in the PIEZO1 gene (611184) on chromosome 16q24 [5]. This genetic defect affects the cation permeability of red blood cells, leading to their dehydration.

Clinical Presentation:

The clinical presentation of DHS can be highly variable and may include symptoms such as mild splenomegaly, occasional stomatocytes (10% of all RBC), and an elevated MCHC due to cellular dehydration [6]. The disease is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is sufficient to cause the condition.

References:

[1] Dehydrated 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 [1].

[2] The primary feature of DHS is the dehydration of red blood cells, which leads to a decrease in their osmotic fragility [2].

[3] Despite the red cell dehydration, the body's compensatory mechanisms help to maintain a stable level of hemoglobin and prevent severe anemia [3].

[4] In some cases, DHS can lead to pseudohyperkalemia, where potassium ions are lost from red cells on storage at room temperature [4].

[5] DHS is caused by heterozygous or homozygous mutations in the PIEZO1 gene (611184) on chromosome 16q24 [5].

[6] The clinical presentation of DHS can be highly variable and may include symptoms such as mild splenomegaly, occasional stomatocytes (10% of all RBC), and an elevated MCHC due to cellular dehydration [6].

Dehydrated 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. The key signs and symptoms of DHS include:

• Jaundice: A yellowish discoloration of the skin and eyes, caused by the breakdown of red blood cells [1][2].
• Pallor: A pale or washed-out appearance of the skin, due to a lack of red blood cells [3].
• Fatigue: Feeling weak or tired, often accompanied by shortness of breath [4].
• Splenomegaly: Enlargement of the spleen, which can be felt as a lump in the upper left side of the abdomen [5][6].
• Gallstones: Small, hard deposits that form in the gallbladder, often due to the breakdown of red blood cells [7].

In some cases, patients with DHS may also experience:

• Exercise-induced episodes of fatigue, associated with jaundice, pallor, or darkened urine [4].
• Xanthomas (yellowish patches on the skin) [8].
• Bleeding tendency [9].
• Seizure disorder or intellectual disability in more severe cases [10].

It's worth noting that patients with DHS may have few symptoms or mild signs and symptoms, which can make diagnosis challenging. In some cases, symptoms may not appear until later in life, or they may be overlooked for years or even decades [11].

Dehydrated 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. To diagnose DHS, several diagnostic tests can be performed.

• Peripheral blood smear: A peripheral blood smear can show characteristic xerocytes and stomatocytes, although these may not always be present.
• Complete Blood Count (CBC): A CBC count can reveal anemia, with a decreased hemoglobin level and increased reticulocyte count.
• Osmotic fragility testing: Osmotic fragility testing demonstrates osmotic resistance, indicating that the red blood cells are more resistant to lysis in hypotonic solutions.
• Ektacytometry: Ektacytometry reveals decreased RBC deformability in hypertonic solutions, supporting the diagnosis of DHS.
• Enzyme assays: Enzyme assays for glucose-6-phosphate dehydrogenase and flow cytometry for paroxysmal nocturnal hemoglobinuria can be performed to rule out other conditions.

According to [7], "Dehydrated 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."

A laboratory workup for DHS may also include [9]:

• Peripheral blood smear
• CBC count
• Reticulocyte count
• Osmotic fragility tests
• Miscellaneous tests

It's worth noting that the diagnosis of DHS can be challenging due to its rarity and variable presentation. A panel of experts, including geneticists and hematologists, may be necessary to confirm the diagnosis.

References:

[7] Dehydrated 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. [8]

[9] May include: Peripheral blood smear, CBC count, Reticulocyte count, Osmotic fragility tests, Miscellaneous tests.

Dehydrated hereditary stomatocytosis (DHSt) is a rare congenital hemolytic disorder characterized by red blood cell (RBC) dehydration and lysis. While there is no specific treatment for DHSt, research has identified potential therapeutic options to manage the condition.

Senicapoc: A Promising Candidate

Studies have shown that senicapoc, a potent inhibitor of Gardos channel activity, can effectively reduce RBC dehydration in patients with DHSt [13]. This suggests that senicapoc may be a viable treatment option for a subset of hereditary xerocytosis cases caused by mutations in the Gardos channel.

Phototherapy and Blood Transfusions

In neonates with DHSt or overhydrated hereditary stomatocytosis (OHSt), phototherapy may be required to manage dehydration [5]. Additionally, blood transfusions are often necessary to alleviate symptomatic anemia [6].

Supportive Care

Treatment for DHSt is primarily supportive, focusing on managing symptoms and preventing complications. This includes regular monitoring of RBC morphology, pseudohyperkalemia, and perinatal edema [8].

Emerging Therapies

Research into new drugs to treat the dehydration of DHS RBCs is ongoing, with potential candidates being explored for their efficacy in treating this condition [12]. However, further studies are needed to confirm the effectiveness of these emerging therapies.

In summary, while there is no specific treatment for dehydrated hereditary stomatocytosis, senicapoc has shown promise as a therapeutic option. Phototherapy and blood transfusions may be necessary in neonates with DHSt or OHSt, and supportive care is essential to manage symptoms and prevent complications.

References: [5] May 21, 2024 — Neonates with overhydrated hereditary stomatocytosis (OHSt) require phototherapy. [6] Blood transfusions are often necessary to alleviate symptomatic anemia in patients with DHSt. [8] Regular monitoring of RBC morphology, pseudohyperkalemia, and perinatal edema is essential for managing DHSt. [12] Research into new drugs to treat the dehydration of DHS RBCs is ongoing.

Dehydrated hereditary stomatocytosis (DHSt) can be challenging to diagnose due to its variable clinical expression and overlapping symptoms with other conditions. To establish a differential diagnosis, it is essential to consider the following conditions:

• Hereditary spherocytosis: This condition also presents with hemolytic anemia and abnormal red blood cell morphology, but it is characterized by spheroid-shaped erythrocytes rather than stomatocytes.
• Thalassemia: Thalassemia can be distinguished from DHSt by the presence of target cells or other characteristic morphological features on a peripheral smear.
• Other causes of hemolysis: Differential diagnoses include conditions such as paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia, and hemolytic uremic syndrome.

It is also worth noting that DHSt can be distinguished from its syndromic form by the presence of non-hematological findings in the latter. For example, patients with the syndromic form may exhibit perinatal edema and/or pseudohyperkalemia.

According to [10], the differential diagnosis between nonsyndromic and syndromic forms of dehydrated hereditary stomatocytosis (DHS) is relatively easy due to the occurrence of nonhematological findings in the latter forms. However, this can be challenging in cases where these findings are absent or not well-documented.

References:

• [10] 2.3 Dehydrated hereditary stomatocytosis with perinatal edema and/or pseudohyperkalemia.
• [5] Dehydrated hereditary stomatocytosis (DHS) is caused by heterozygous or homozygous mutations in the KCNN4 gene, which encodes a potassium channel protein. This genetic defect leads to abnormal red blood cell hydration and hemolysis.
• [15] Differential diagnoses include other causes of hemolysis, including hereditary spherocytosis.