Hereditary Neutrophilia - Diagnosis and Its treatment.

What Is Hereditary Neutrophilia?

It is a form of lifelong, persistent neutrophilia. Hereditary neutrophilia is a condition characterized by an increase in the number of neutrophils in the blood. 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.

The other synonyms of hereditary neutrophilia include:

• Neutrophilia.

• Disorders with increased neutrophil counts.

• Leukocytosis.

What Are Neutrophils?

Neutrophils are granulocytes that comprise an important component of the immune defenses that are non-specific. Their main function is phagocytosis (ingestion of microbes). They attract other white blood cells, derive their biogenesis from pleuripotent stem cell progenitors in the bone marrow.

How Are the Mature Neutrophils Formed?

Neutrophil production takes place in the bone marrow of humans. The life cycle of a neutrophil can be subdivided into the bone marrow, blood, and tissue phases. The following forms of myeloblast, promyelocyte, and myelocyte are capable of cell division and differentiation. These three forms comprise the mitotic compartment. The metamyelocyte, the band cells, and the polymorphonuclear cells are the more mature forms of neutrophils and they are incapable of cell division, but they do undergo cell maturation and differentiation. These other three forms of neutrophil cells constitute the maturation compartment and flow into the blood. These forms are distributed into either the circulating granulocyte pool (CGP) or the marginal granulocyte pool (MGP). The total blood granulocyte pool (TBGP) is the sum of the circulating granulocyte pool and the marginal granulocyte pool. The cells have to maintain a constant equilibrium in these two pools. These two pools are approximately equal in size.

Pleuripotent stem cell progenitors upon stimulation by colony-stimulating factors convert into myeloblasts. These myeloblasts are capable of cell multiplication and differentiation. They then differentiate into promyelocyte. These cells are also capable of cell division and differentiate into myelocytes. Myelocytes are also capable of cell multiplication and differentiation. However, after this form, the cells lose their ability to divide. Myelocytes differentiate into metamyelocytes which are incapable of cell division. Then, the band cells are formed that are also incapable of cell division. They then transform into mature segmented polymorphonuclear neutrophils that are also incapable of cell division.

What Is the Etiopathogenesis of Hereditary Neutrophilia?

The disorder primarily occurs due to persistently increased counts of mutated (abnormal) segmented neutrophils. There is a heterozygous genetic mutation in the colony-stimulating factor 3 receptor (CSF3R) gene located on chromosome 1p34. A number sign (#) is denoted to this entity because of the fact that hereditary neutrophilia occurs due to a heterozygous mutation in the CSF3R gene on chromosome 1p34. The condition is reported to be an autosomal dominant hereditary disorder.

What Is the Epidemiology of Hereditary Neutrophilia?

• Prevalence: Less than 1/1000000 (worldwide).

• Age Of Onset: Seen at all ages.

• Life Expectancy: Normal life expectancy is usually seen.

What Are the Clinical Signs and Symptoms of Hereditary Neutrophilia?

Patients suffering from hereditary neutrophilia are predominantly asymptomatic but may occasionally exhibit symptoms associated with the systemic inflammatory response reaction. These include:

• Fever.

• Weight loss.

• Anemia.

• Unhealed sores.

• Feeling dizzy.

• Dyspnea (difficulty in breathing).

• Tachycardia (increased heart rate).

• Pleural and pericardial effusion (excessive collection of fluid in heart and lungs).

• Myelodysplastic syndrome (a group of cancers where the immature blood cells in the bone marrow fail to mature or develop into healthy blood cells).

• Polydipsia (feeling of extreme thirstiness).

• Muscle weakness.

• Hepatosplenomegaly (liver and spleen enlargement).

• Widened skull dipole (The diploic space is a medullary cavity of the skull. It is the place where normal physiologic hematopoiesis in adults takes place. Thus, bilateral expansion of this structure is usually seen in hereditary neutrophilia cases).

What Is a Normal Neutrophil Count?

The neutrophil count in a healthy individual can vary depending on factors such as the age of the patient. Usually, a normal level of neutrophil count is 1,450 to 7,500 neutrophils per microliter. Neutrophilia occurs when the patient has more than 7,500 neutrophils per microliter. Leukocytosis is likely to happen when the patient has more than 11,000 total white cells per microliter.

What Are the Diagnostic Findings of Hereditary Neutrophilia?

The following findings may appear on performing diagnostic tests.

• It is important to take a blood smear for all hematological diseases.

• Patient examination and complete medical history are very important to rule out other diseases.

• The neutrophil count is elevated. The segmented polymorphonuclear neutrophils are morphologically and functionally normal.

• Segmented polymorphonuclear neutrophils or band cells are greater than 70 percent and less than 10 percent immature granulocytes.

• Serum alkaline phosphatase elevated.

• Thickened calvarium (the portion of a skull including the braincase. It either excludes the lower jaw or both the lower jaw and facial portion.)

• Hepatosplenomegaly (enlarged liver and enlarged spleen).

• Elevated leukocyte alkaline phosphatase.

• Elevated serum vitamin B12 levels.

• Bone marrow analysis usually shows an increase in granulocyte precursors.

• Bone marrow aspirate might show marked dysgranulopoiesis but no dyserythropoiesis (defective or abnormal development of red blood cells) or dysmegakaryopoiesis (more than or equal to 10 percent of dysplastic megakaryocytes in the blood smear of the patient).

• Cytogenetic analysis revealed a clonal abnormality (chromosome 3q26 deletion) in more than 70 percent of metaphases. Genetic tests for the genes can also be done.

• Histiocytes of the gaucher type (a type of lysosomal storage disease where there is an accumulation of large quantities of fat or lipids) may also be seen.

What Is the Treatment of Hereditary Neutrophilia?

Treatment of neutrophilia where the white blood cell count exceeds the count of 50,000 demands aggressive hydration and cytotoxic therapy with hydroxyurea. Cytotoxic therapy is a treatment modality that is used to kill cancer (malignant or dysplastic) cells by using anticancer drug preparations, including the use of botanical agents along with anticancer drugs (chemotherapy). Drugs like Methylprednisolone Succinate, Methylprednisolone, and Prednisolone Phosphate have been approved to cure hereditary neutrophilia.

Conclusion

Hereditary neutrophilia is a very rare genetic disorder that causes chronic neutrophilia in individuals. It can lead to hepatosplenomegaly. The patient should immediately contact the healthcare professional for the treatment of this disorder. The prognosis is good for this disorder. More research should be conducted on this disorder involving a larger clinical sample.