severe congenital neutropenia 5

Severe Congenital Neutropenia: A Rare and Serious Condition

Severe congenital neutropenia, also known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis. This condition causes a congenital form of neutropenia, usually without other physical malformations.

Key Features:

• Congenital: Present at birth
• Neutropenia: Low levels of neutrophils, a type of white blood cell essential for fighting infections
• Severe: Markedly chronic neutropenia and a predisposition to MDS (Myelodysplastic Syndrome) and leukemia

Symptoms:

• Life-threatening bacterial infections in infancy
• Severe pyogenic infections

Causes: Autosomal dominant inheritance of mutations can cause severe congenital neutropenia.

Note: The information provided is based on the context [10] and [11].

Frequent Infections and Fevers

People with severe congenital neutropenia experience bacterial infections early in life, which can cause inflammation of the umbilical cord stump, abscesses (or boils) on the skin, oral infections, and pneumonia. These infections often lead to recurring fevers, making it a common symptom of this condition.

• Inflammation of the umbilical cord stump: This is a diagnostic clue that could be present in neonates.
• Abscesses or boils on the skin: These can occur due to bacterial infections.
• Oral infections: People with SCN are prone to oral infections, which can cause mouth sores (ulcers).
• Pneumonia: Respiratory symptoms, including signs of pneumonia, can also be a sign of severe congenital neutropenia.

These symptoms often become evident early in life and can be life-threatening if left untreated. [5][6][9]

Diagnostic Tests for Severe Congenital Neutropenia

Severe congenital neutropenia (SCN) can be diagnosed through a combination of clinical evaluation, laboratory tests, and genetic analysis. The following diagnostic tests are commonly used to determine the presence and severity of SCN:

• Complete Blood Count (CBC): A CBC is essential for diagnosing SCN. It measures the number of white blood cells, including neutrophils, in the blood. In individuals with SCN, the neutrophil count is typically very low (<0.5 G/l) [8][10].
• Bone Marrow Biopsy: A bone marrow biopsy can be helpful in confirming a diagnosis of SCN. The procedure involves taking a sample of bone marrow from the hipbone and examining it under a microscope for signs of abnormal neutrophil development [3][13].
• Genetic Testing: Targeted sequence testing is offered to detect mutations in genes such as ELANE and HAX1, which can help confirm a diagnosis of congenital or cyclic neutropenia [2]. This test is particularly useful when there is a family history of SCN.
• Bone Marrow Examination with Cytogenetics: A bone marrow examination with cytogenetic analysis can also be performed to rule out malignant conditions that may mimic SCN, such as acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) [7][11].

These diagnostic tests are essential for accurately diagnosing severe congenital neutropenia and determining the underlying cause of the condition.

Treatment Options for Severe Congenital Neutropenia

Severe congenital neutropenia (SCN) is a rare genetic disorder characterized by a significant reduction in the number of neutrophils, a type of white blood cell that plays a crucial role in fighting infections. In such cases, drug treatment is often necessary to manage the condition.

Daily Subcutaneous G-CSF Administration

One of the most effective treatments for SCN is daily subcutaneous administration of Granulocyte-Colony Stimulating Factor (G-CSF). This medication stimulates the production of neutrophils in the bone marrow, leading to an increase in blood neutrophil count and a reduction in the number of infections.

• Dosage: The dosage of G-CSF is typically titrated to maintain an adequate absolute neutrophil count (ANC).
• Effectiveness: Daily subcutaneous G-CSF administration has been shown to be highly effective in increasing blood neutrophils count and reducing the frequency of infections in patients with SCN.

References

• [5] by J Skokowa · 2017 · Cited by 371 — Daily subcutaneous G-CSF administration is the treatment of choice and leads to a substantial increase in blood neutrophils count, reduction of ...

Differential Diagnosis of Severe Congenital Neutropenia

Severe congenital neutropenia (SCN) is a rare hematological condition characterized by impaired myeloid precursor differentiation or function. When diagnosing SCN, it's essential to consider other conditions that may present with similar symptoms. The differential diagnosis for SCN includes:

• Cyclic Neutropenia: An autosomal dominant disorder characterized by oscillating numbers of blood neutrophils, monocytes, platelets, and reticulocytes.
• Myelodysplastic Syndrome (MDS): A group of disorders caused by poorly formed or dysfunctional blood cells, which can lead to severe anemia, infections, and bleeding.
• Acute Myelogenous Leukemia (AML): A type of cancer that affects the bone marrow and blood, characterized by the rapid growth of abnormal white blood cells.
• Common Variable Immunodeficiency (CVID): A rare genetic disorder that impairs the immune system's ability to fight infections.
• Other Congenital Neutropenic Disorders: Such as Kostmann syndrome, which is a severe congenital neutropenia associated with defective expression of Bcl-2 and excessive apoptosis of myeloid cells.

These conditions can be challenging to differentiate from SCN, especially in the early stages. A thorough medical evaluation, including blood tests and bone marrow examination, is necessary to determine the underlying cause of neutropenia.

References:

• [5] The congenital neutropenia syndromes are rare haematological conditions defined by impaired myeloid precursor differentiation or function.
• [10] The differential diagnosis of congenital neutropenia 10 includes a number of congenital and acquired diseases.
• [13] This suggests that one should consider immune neutropenia in the differential diagnosis of severe acquired neutropenia, even in the absence of a specific syndrome.