congenital nonspherocytic hemolytic anemia

Congenital Nonspherocytic Hemolytic Anemia (CNSHA) is a group of rare genetic disorders characterized by the premature destruction of red blood cells, leading to chronic and sometimes severe anemia.

• Causes: CNSHA is caused by defects in various enzymes involved in red blood cell metabolism, such as glucose-6-phosphate dehydrogenase (G6PD), pyruvate kinase, and glucose-6-phosphate isomerase [1, 5, 10].
• Symptoms: The main features of CNSHA include jaundice, pallor, fatigue, and anemia due to the increased breakdown of red blood cells [4, 12].
• Types: There are several types of CNSHA, including:
  • Congenital nonspherocytic hemolytic anemia-1 (CNSHA1), caused by G6PD deficiency [1, 6, 15]
  • Congenital nonspherocytic hemolytic anemia-2 (CNSHA2), caused by pyruvate kinase deficiency [14]
  • Congenital nonspherocytic hemolytic anemia-9 (CNSHA9), an X-linked hematologic disorder characterized by mild to moderate red cell anemia [11, 13]
• Treatment: Treatment for CNSHA typically involves symptomatic management of the anemia and may include blood transfusions, iron supplements, and other supportive measures [4].

References:

[1] Description. Congenital nonspherocytic hemolytic anemia-1 (CNSHA1), caused by mutation in the G6PD gene, is the most common genetic form of chronic and drug-, food-, or infection-induced hemolytic anemia.

[5] by GC DE GRUCHY · 1960 · Cited by 86 — The clinical and hematological features of seven cases of nonspherocytic congenital hemolytic anemia occurring in four different families are presented

[10] Any one of a group of congenital hemolytic anemias that is caused by defects of glycolysis in the erythrocyte.

[4] Description. Red cell pyruvate kinase deficiency, or congenital nonspherocytic hemolyic anemia-2 (CNSHA2), is the most common cause of hereditary nonspherocytic hemolytic anemia.

[11] Description. Congenital nonspherocytic hemolytic anemia-9 (CNSHA9) is an X-linked hematologic disorder characterized by onset of mild to moderate red cell anemia soon after birth or in childhood.

[13] Disorders of erythrocyte metabolism have been included in the term congenital nonspherocytic hemolytic anemia (CNSHA), a classification that traditionally includes erythrocyte disorders not due to defects of hemoglobin, the membrane, immune-mediated disease, or other diseases such as paroxysmal nocturnal hemoglobinuria.

Common Signs and Symptoms

Congenital nonspherocytic hemolytic anemia (CNSHA) is a rare condition characterized by the premature destruction of red blood cells. The signs and symptoms of CNSHA can vary in severity and duration, but common manifestations include:

• Fatigue: People with CNSHA may experience persistent tiredness or weakness due to anemia [1][2].
• Pallor: Unusually pale skin (pallor) is a common sign of CNSHA, resulting from the lack of red blood cells [3][4].
• Jaundice: Yellowing of the eyes and skin (jaundice) can occur due to the buildup of bilirubin in the body [5][6].
• Splenomegaly: Enlargement of the spleen (splenomegaly) may be present, which can lead to discomfort or pain in the upper left region of the abdomen [7][8].
• Dark yellow urine: CNSHA can cause dark yellow urine due to the presence of bilirubin [9].

Other Possible Symptoms

In some cases, people with CNSHA may experience more severe symptoms, including:

• Hypoxia: Insufficient oxygen supply to tissues and organs
• Hypovolemic shock: Severe blood loss leading to low blood pressure
• Congestive heart failure: Heart failure due to the increased workload from anemia
• Seizures: Rarely, CNSHA can cause seizures in severe cases [10][11].

Important Note

It's essential to consult a healthcare professional for an accurate diagnosis and treatment plan. The symptoms of CNSHA can be similar to those of other conditions, making it crucial to undergo proper medical evaluation and testing.

References:

[1] Congenital hemolytic anemia (CHA) is a diverse group of rare hereditary conditions marked by decreased life expectancy and premature removal of erythrocytes from blood flow. [2] [3] Signs and Symptoms of Hemolytic Anemia · Fatigue, Pallor, Jaundice, Splenomegaly, Dark yellow urine [4] The constellation of signs and symptoms that occur in conjunction with the anemia are critical for the evaluation. [5] Often termed congenital nonspherocytic hemolytic anemia (CNSHA), this group includes disorders not due to immune ... [6] Any one of a group of congenital hemolytic anemias in which there is no abnormal hemoglobin or spherocytosis and in which there is a defect of glycolysis in the erythrocyte. [7] The group of enzymopathies, glycolytic pathway enzyme deficiencies, is termed the congenital nonspherocytic hemolytic anemias (CNSHAs) as these deficiencies have no characteristic morphology on blood smear.

Diagnostic Tests for Congenital Nonspherocytic Hemolytic Anemia

Congenital nonspherocytic hemolytic anemia (CNSHA) is a group of disorders characterized by chronic hemolysis, and the diagnostic approach involves a step-wise testing process. The following tests are used to diagnose CNSHA:

• Red Blood Cell Morphology: This test examines the shape and size of red blood cells. In CNSHA, red blood cell morphology is essentially normal [5].
• Blood Tests: A complete blood count (CBC) is performed to evaluate the number and characteristics of red blood cells, white blood cells, and platelets.
• Urine Tests: Urine tests may be conducted to rule out other conditions that can cause hemolysis.
• Bone Marrow Biopsy and Aspiration: This test involves taking a sample of bone marrow tissue for examination under a microscope. It helps to identify any abnormalities in the production of red blood cells [6].
• Genetic Testing: Genetic testing is used to detect single nucleotide and copy number variants in 37 genes associated with hereditary hemolytic anemia [7]. This test utilizes next-generation sequencing technology.
• Osmotic Fragility Test: This test measures the fragility of red blood cells when exposed to different concentrations of salt solutions. It helps to diagnose conditions such as G6PD deficiency and other enzymatic disorders [2].
• Eosin-5-maleimide (EMA) Flow Cytometry: EMA binding or osmotic fragility testing may be used to diagnose CNSHA, especially in cases where the osmotic fragility test is normal [14].

Additional Tests

In some cases, additional tests such as:

• Reticulocyte Count: This test measures the number of reticulocytes (immature red blood cells) in the blood.
• Serum Bilirubin and Van den Bergh Test: These tests measure the levels of bilirubin in the blood, which can indicate hemolysis.

These diagnostic tests help to confirm the diagnosis of CNSHA and rule out other conditions that may cause similar symptoms. The specific tests used may vary depending on the individual case and the suspected underlying cause of the condition.

References:

[1] Mansour-Hendili L et al. (2020) Diagnosis of congenital nonspherocytic hemolytic anemia: A review of the literature [3]. [2] Kim Y et al. (2017) Diagnostic approach to hereditary hemolytic anemias [2]. [5] G6PD deficiency topic review discusses the clinical manifestations, diagnosis, and management of G6PD deficiency [15].

Treatment Options for Congenital Nonspherocytic Hemolytic Anemia

Congenital nonspherocytic hemolytic anemia (CNSHA) is a rare genetic disorder characterized by chronic and drug-, food-, or infection-induced hemolytic anemia. While there is no cure, various treatment options are available to manage the condition.

• Pharmacological Treatment: In some cases, pharmacological treatment may be necessary to reduce hyperbilirubinemia. For example, long-term phenobarbital treatment has been shown to permanently reduce hyperbilirubinemia in patients with congenital non-spherocytic hemolytic anemia [2].
• Blood Transfusions: Blood transfusions may be required to manage severe anemia. However, this approach is typically reserved for acute episodes and not as a long-term solution.
• Splenectomy: In some cases, splenectomy may be recommended, particularly in children who receive frequent transfusions or experience daily symptoms related to chronic anemia [14].
• Disease-Modifying Therapies: Newer disease-modifying therapies such as luspatercept and sotatercept are being explored for the treatment of beta-thalassemia, which may also be beneficial for patients with CNSHA [9].

Specific Medications

Certain medications have been used to manage symptoms associated with CNSHA:

• Folic Acid: Prophylactic folic acid is often recommended due to the risk of folate deficiency and megaloblastosis in patients with active hemolysis [4].
• Corticosteroids: Corticosteroids such as prednisone are commonly used to treat autoimmune hemolytic anemia, which can be a complication of CNSHA [6].
• Rituximab: Rituximab has been used to treat autoimmune hemolytic anemia in some cases [4].

Emerging Therapies

Newer therapies such as mitapivat, an allosteric activator of pyruvate kinase, have shown promise in treating pyruvate kinase deficiency (PKD), a type of CNSHA [5]. Additionally, glucocorticoids and IVIG are being explored for the treatment of autoimmune hemolytic anemia associated with CNSHA [6].

It is essential to consult a hematologist to determine the best course of treatment for individual patients.

Differential Diagnosis of Congenital Nonspherocytic Hemolytic Anemia

Congenital nonspherocytic hemolytic anemia (CNSHA) is a group of disorders characterized by ineffective erythropoiesis, chronic extravascular hemolysis, decreased erythrocyte life span, splenomegaly, jaundice, biliary lithiasis, and iron overload [8]. The differential diagnosis of CNSHA involves ruling out other causes of anemia, including conditions that diminish red cell production or increase red cell destruction.

Causes to Consider

• Disorders of erythrocyte metabolism: These include glucose-6-phosphate dehydrogenase deficiency (G6PD), pyruvate kinase deficiency (PKD), and other enzymopathies [13].
• Immune-mediated disturbances: Such as autoimmune hemolytic anemia, which can present with similar symptoms to CNSHA.
• Thalassemia and sickle cell disease (SCD): These genetic disorders can also cause chronic hemolysis and anemia.
• Erythrocyte membrane disorders: Such as hereditary spherocytosis, which can mimic the clinical presentation of CNSHA.

Laboratory Values

The diagnosis of CNSHA is often supported by laboratory values, including:

• Elevated reticulocyte count: Indicating increased red cell production in response to hemolysis.
• Anemia and jaundice: Commonly observed in patients with CNSHA.
• Splenomegaly: Enlargement of the spleen due to chronic hemolysis.

Clinical Management

The clinical management of CNSHA involves a high index of suspicion, careful review of patient history, and laboratory evaluation. A timely differential diagnosis is crucial for appropriate treatment and management [2].

References:

[1] by Y Kim · 2017 · Cited by 80 [8] by ME Conrad · 1960 · Cited by 24 [13] Anemia in the Neonate: The Differential Diagnosis and Treatment Pediatr Ann. 2015 Jul;44(7):e159-63. [2] Haley K. Congenital Hemolytic Anemia. Med. Clin ...