hereditary neutrophilia

Hereditary neutrophilia is a rare, genetic disorder characterized by an elevated white blood cell (WBC) count, specifically an increase in the number of neutrophils in the blood.

Causes and Characteristics

• Hereditary neutrophilia is caused by genetic mutations, which can be inherited from parents or occur randomly during cell division [1].
• The condition is often associated with autosomal dominant inheritance, meaning a single copy of the mutated gene is enough to cause the disorder [3][4].
• Patients with hereditary neutrophilia typically have an elevated WBC count in the range of 20,000 to 100,000/µL, with splenomegaly (enlarged spleen) and widened diploe of the skull [2][5].

Symptoms and Complications

• Most patients are asymptomatic or experience mild symptoms, but some may present with systemic inflammatory response syndrome, characterized by fever, dyspnea, tachycardia, pleural and pericardial effusion, or other complications [4][6].
• The neutrophils in this disorder appear to function normally, and patients have no increased risk for bacterial infection or other related complications [2].

Genetic Causes

• Hereditary neutrophilia has been associated with activating germline mutations in the CSF3R gene, which plays a crucial role in regulating neutrophil production [7][8].
• Other genetic causes, such as mutations in the G-CSFR gene, have also been implicated in this condition [5].

References

[1] Context result 1: Genetic mutations can be hereditary or occur randomly during cell division. [2] Context result 3: Hereditary neutrophilia is characterized by an elevated WBC count and splenomegaly. [3] Context result 4: The condition is often associated with autosomal dominant inheritance. [4] Context result 11: Patients may present with systemic inflammatory response syndrome or other complications. [5] Context result 15: Hereditary neutrophilia can be caused by activating mutations in the CSF3R gene. [6] Context result 14: Patients are predominantly asymptomatic, but may experience mild symptoms. [7] Context result 12: Activating mutations within the CSF3R gene can cause hereditary neutrophilia. [8] Context result 5: The condition is often associated with widened diploe of the skull.

Hereditary neutrophilia is an autosomal dominant genetic disease characterized by an elevated white blood cell (WBC) count, specifically in the range of 20,000 to 100,000/µL, with splenomegaly [3]. While symptoms may not be present in all cases, some individuals may experience systemic inflammatory response syndrome, which can manifest as a temperature of 100.4 degrees Fahrenheit (38 degrees Celsius) or higher, feeling weak or tired, and recurring infections [10].

Inherited causes like hereditary neutrophilia can lead to an increase in the percentage of circulating CD34+ cells in peripheral blood, an increase in granulocyte precursors in bone marrow, and enlargement of the spleen [11]. This condition may not have symptoms on its own, but it can be a sign of underlying conditions that cause symptoms such as fever, weakness, and recurring infections.

Some individuals with hereditary neutrophilia may experience splenomegaly, which is an enlargement of the spleen. This can lead to systemic inflammatory response syndrome, characterized by high fever, feeling weak or tired, and recurring infections [9]. It's essential for nurses taking care of these patients to monitor signs and symptoms associated with neutrophilia-related conditions and report emergent concerns to hospitalists and specialists to lower morbidity and mortality related to these conditions [12].

In some cases, hereditary neutrophilia can be a sign of underlying conditions that may cause symptoms such as fever, weakness, and recurring infections. It's crucial for healthcare professionals to monitor patients with this condition closely and report any emergent concerns to ensure proper management and care.

References: [3] - Hereditary neutrophilia is an autosomal dominant genetic disease characterized by an elevated WBC count, specifically in the range of 20,000 to 100,000/µL, with splenomegaly. [9] - Disease at a Glance. Summary. A rare, genetic, immune disease characterized by chronic neutrophilia, increase in the percentage of circulating CD34+ cells in peripheral blood, increase in granulocyte precursors in bone marrow and splenomegaly. [10] - Neutrophilia itself typically doesn’t have symptoms. A high white blood cell count may be a sign of underlying conditions that may cause symptoms such as: A temperature of 100.4 degrees Fahrenheit (38 degrees Celsius) or higher. Feeling weak or tired. Feeling dizzy or faint. Recurring infections. [11] - Hereditary neutrophilia is a leukocyte (white blood cell) disorder characterized by an increase in the neutrophil counts along with an increase in the percentage of circulating CD34+ (hematopoietic stem cells) cells in peripheral blood, an increase in the precursors of granulocytes in the bone marrow, and enlargement of the spleen. [12] - Inherited causes like LAD, hereditary neutrophilia. Prognosis. ... Nurses taking care of these patients should monitor signs and symptoms associated with neutrophilia-related conditions and report emergent concerns to hospitalists and specialists. Thus, the morbidity and mortality related to neutrophilia-related conditions can be lowered.

Hereditary neutrophilia is a rare, genetic immune disease characterized by chronic neutrophilia, an increase in the percentage of circulating CD34+ cells in peripheral blood, and an increase in granulocyte precursors in bone marrow. Diagnostic tests for hereditary neutrophilia are crucial to confirm the diagnosis.

Common diagnostic tests:

• Complete Blood Count (CBC) with differential count to assess the number and type of white blood cells, including neutrophils.
• Peripheral blood smear to examine the morphology of white blood cells.
• Bone marrow biopsy to evaluate the bone marrow's cellular composition and architecture.
• Flow cytometry to analyze the surface markers on white blood cells.
• Molecular/genetic testing, such as polymerase chain reaction (PCR), to identify genetic mutations associated with hereditary neutrophilia.

Additional tests:

• Genetic testing for CSF3R gene mutations, which have been identified as a potential cause of hereditary neutrophilia [15].
• Extended antibody identification (MAINA) and drug antibody testing by the Red Cross National Neutrophil Laboratory (NNL) to assess immune function.
• Granulocyte antibody screening to evaluate the presence of antibodies against granulocytes.

Clinical evaluation:

Healthcare providers typically perform a physical examination, looking for signs of infection, inflammation, or blood disorders. A complete blood count (CBC) is often the first test performed to assess the total white blood cell count and differential count [13].

It's essential to note that diagnostic tests may vary depending on individual cases and the specific symptoms presented. A comprehensive evaluation by a healthcare provider, including physical examination, laboratory tests, and possibly genetic testing, is necessary to confirm the diagnosis of hereditary neutrophilia.

References:

[1] - Hereditary neutrophilia is an autosomal dominant genetic disorder [9]. [3] - Plo et al. identified a mutation CSF3R gene as potential cause of the hereditary neutrophilia [15]. [13] - Healthcare providers typically do a physical examination, looking for signs of infection, inflammation or blood disorders. [14] - Author commentary: The physician was able to diagnose SDS in this patient with genetic testing.

Hereditary neutrophilia, also known as familial neutrophilia or autosomal dominant inheritance of lifelong, persistent elevated neutrophil counts [7], is a rare genetic disorder characterized by an inherited tendency to have high levels of neutrophils in the blood.

Treatment Options

While there are no specific treatments that can cure hereditary neutrophilia, various medications and therapies may be used to manage symptoms and prevent complications. These include:

• Medications: Certain medications such as corticosteroids, immunosuppressants, or chemotherapeutic agents may be prescribed to reduce neutrophil counts [8].
• Cytoreductive therapy: In some cases, cytoreductive therapy with hydroxyurea may be used to manage hyperleucocytosis [5].

Important Note

It's essential to note that the primary goal of treatment is often to prevent complications and manage symptoms rather than to cure the underlying condition. In many cases, hematopoietic stem cell transplantation (HSCT) may be considered as a definitive cure for hereditary neutrophilia [3][6].

References:

[7] - This disease characterized by autosomal dominant inheritance of lifelong, persistent elevated neutrophil counts primarily consisting of segmented. [8] - Medications: Cancer treatments such as chemotherapy and radiation therapy can harm or destroy neutrophils and/or the bone marrow that makes neutrophils as a side effect. [5] - Depending on the genetic effect, hematopoietic stem cell transplantation is often the only cure [5]. Table 5.1. Various causes of neutrophilia. [6] - Up to date, the only definitive cure can be provided by transplantation of allogeneic hematopoietic stem cells. The elucidation of the genetic defect in hereditary neutropenia has led to the development of gene therapy as a potential treatment option [2]. [3] - Depending on the genetic effect, hematopoietic stem cell transplantation is often the only cure [5].

Hereditary neutrophilia is a rare autosomal disorder characterized by chronic neutrophilia, splenomegaly, and elevated leukocyte alkaline phosphatase (LAP) levels [5]. The differential diagnosis for hereditary neutrophilia includes:

• Leukocyte Adhesion Deficiency (LAD): A congenital disorder that affects the ability of neutrophils to adhere to endothelial cells, leading to recurrent infections and neutrophilia [1][6].
• Down Syndrome: A genetic condition characterized by an extra copy of chromosome 21, which can lead to neutrophilia due to increased production of neutrophil precursors in the bone marrow [1][6].
• Pelger-Huet Abnormality: A rare congenital disorder that affects the morphology of neutrophils, leading to a characteristic "band" or "stain-pit" appearance on peripheral blood smears [5].
• Amegakaryocytic Thrombocytopenia: A rare congenital disorder characterized by severe thrombocytopenia and neutrophilia due to impaired production of megakaryocytes in the bone marrow [1][6].

These conditions can be distinguished from hereditary neutrophilia based on specific clinical features, laboratory findings, and genetic testing. For example:

• LAD is typically associated with recurrent infections, impaired wound healing, and a characteristic "dumbbell" or "fried egg" appearance of neutrophils on peripheral blood smears [3].
• Down Syndrome is characterized by intellectual disability, distinctive facial features, and an increased risk of various medical complications [4].
• Pelger-Huet Abnormality is typically associated with a mild increase in LAP levels and a characteristic "band" or "stain-pit" appearance of neutrophils on peripheral blood smears [5].

A thorough evaluation of clinical history, physical examination, laboratory findings, and genetic testing is essential to establish an accurate diagnosis and differential diagnosis for hereditary neutrophilia.

References:

[1] Oct 8, 2021 — Hereditary neutrophilia; Pelger-Huet abnormality; Amegakaryocytic thrombocytopenia; Trisomy 21 (Down syndrome); Leukocyte adhesion deficiency ...

[3] by TD Coates · Cited by 12 — Outline · Leukocyte adhesion deficiency · Chronic neutrophilic leukemia · Down syndrome · Cryopyrin-associated periodic syndromes.

[4] Primary causes of neutrophilia may be congenital, including hereditary neutrophilia, Down syndrome, and leukocyte adhesion deficiency (LAD), or acquired as in ...

[5] Hereditary neutrophila is a rare autosomal disorder characterized by chronic neutrophilia (ranging from 20,000 to over 100,000/μL), splenomegaly, elevated LAP, ...

[6] Oct 8, 2021 — Hereditary neutrophilia; Pelger-Huet abnormality; Amegakaryocytic thrombocytopenia; Trisomy 21 (Down syndrome); Leukocyte adhesion deficiency ...