severe congenital neutropenia 7

Severe Congenital Neutropenia (SCN) Description

Severe congenital neutropenia, also known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis. Myelopoiesis refers to the process by which the bone marrow produces white blood cells, including neutrophils.

Characteristics of SCN

• Affects myelopoiesis, leading to low levels of neutrophils
• Rare and inherited disorders
• Marked chronic neutropenia (low neutrophil count)
• Predisposition to Myelodysplastic Syndromes (MDS) and leukemia

Key Points

• SCN is a rare genetic condition that affects the production of white blood cells.
• It leads to low levels of neutrophils, making individuals prone to infections.
• The disorder can also increase the risk of developing MDS or leukemia.

[7]

Early Signs and Symptoms of Severe Congenital Neutropenia

Severe congenital neutropenia, also known as Kostmann syndrome, is a rare genetic disorder that affects the production of white blood cells. The condition typically manifests in infancy with life-threatening bacterial infections.

• Frequent Infections: People with SCN experience frequent infections, most often in the mouth, throat, sinuses, skin, and lungs.
• Fever: Frequent fevers are a common symptom of SCN.
• Respiratory Symptoms: Children with SCN may develop respiratory symptoms, including signs of pneumonia.
• Umbilical Infection: In some cases, an acute and severe umbilical infection can occur within the first days of life.

These symptoms often become evident early in life, and if left untreated, can lead to serious complications. It's essential for parents or caregivers to seek medical attention promptly if they suspect that their child is experiencing any of these symptoms.

References:

• [7] - Severe Chronic Neutropenia, including symptoms, causes, and treatments.
• [11] - Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations.

Diagnostic Tests for Severe Congenital Neutropenia

Severe congenital neutropenia (SCN) can be diagnosed through various tests, including:

• Targeted sequence testing: This test is used to detect mutations in the ELANE and HAX1 genes, which can help confirm a diagnosis of congenital or cyclic neutropenia. [7]
• Bone marrow biopsy: A bone marrow biopsy can be very helpful in the diagnosis of SCN. It helps rule out malignant conditions and provides information on the number of early myeloid precursors and mature neutrophils. [9, 14]
• Blood tests: Blood tests that include a full blood count can determine the number of neutrophils, which is often low in individuals with SCN. [1]
• Bone marrow aspirate and cytogenetics: This test is recommended for patients with SCN to evaluate their bone marrow before treatment and annually thereafter. [12]

It's worth noting that the diagnosis of SCN typically involves a combination of these tests, as well as a physical exam and symptom check. A physician may also order additional tests to rule out other conditions that can cause neutropenia.

References:

[7] Targeted sequence testing is offered for the detection of mutations in the ELANE and HAX1 genes, which can help confirm a diagnosis of congenital or cyclic neutropenia. [9] Bone marrow biopsy can be very helpful in the diagnosis of severe congenital neutropenia. Bone marrow is also necessary to rule out malignant conditions. [14] Clinically, examination of the bone marrow is the most important diagnostic test for evaluating severe congenital neutropenia.

Treatment Options for Severe Congenital Neutropenia

Severe congenital neutropenia (SCN) is a rare genetic disorder characterized by a significant reduction in the production of white blood cells, making patients prone to recurrent infections. While there are various treatment options available, the primary goal is to prevent and manage infections.

Mavorixafor: A Newer Medication

One of the newer medications being investigated for SCN is Mavorixafor (7). Originally used to treat neutropenia in other conditions, this medication has shown promise in increasing the neutrophil count and reducing infection rates in patients with SCN. While more research is needed to fully understand its efficacy and potential side effects, Mavorixafor may offer a new treatment option for patients with SCN.

Other Treatment Options

In addition to Mavorixafor, other treatment options for SCN include:

• G-CSF (Granulocyte-Colony Stimulating Factor): This medication has been used successfully to increase the neutrophil count and reduce infection rates in patients with SCN (5, 8). G-CSF works by stimulating the production of white blood cells.
• Hematopoietic Stem Cell Transplantation: In some cases, a bone marrow transplant may be necessary to replace the faulty stem cells responsible for SCN (13).
• Investigational Therapies: Researchers are also exploring other potential treatments, such as GM-CSF and investigational medications like Mavorixafor.

Important Considerations

It's essential to note that each patient with SCN is unique, and treatment plans should be tailored to individual needs. Patients with mild neutropenia may continue treatment if the drugs are otherwise improving their symptoms (12). However, those who develop early neutropenia while taking medications known to cause agranulocytosis at high rates should discontinue taking the drug immediately.

References:

• [7] Mavorixafor is a newer medication under investigation for severe congenital and idiopathic neutropenia.
• [5] Daily subcutaneous G-CSF administration is the treatment of choice and leads to a substantial increase in blood neutrophils count, reduction of infections, and improvement in quality of life.
• [8] G-CSF has been used with success for increasing the ANC and decreasing the number of infections in patients with severe congenital neutropenia (Bonilla et al, ...).
• [13] Treatment for severe congenital neutropenia focuses on preventing and managing infections.

Differential Diagnosis of Severe Congenital Neutropenia

Severe congenital neutropenia (SCN) is a rare genetic disorder characterized by low levels of granulocytes in the blood. The differential diagnosis of SCN involves ruling out other conditions that may present with similar symptoms.

• Cyclic Neutropenia: This is an autosomal dominant congenital neutropenia characterized by oscillating levels of neutrophils, monocytes, lymphocytes, platelets, and reticulocytes on a 21-day cycle.
• Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome: SCN is associated with an increased risk of developing AML and myelodysplastic syndrome.
• Common Variable Immunodeficiency: This is the most common immunodeficiency encountered, but it can present with different symptoms than SCN.

Other Conditions to Consider

• Infectious Causes: Bacterial sepsis, viral infections (such as cytomegalovirus), and fungal infections can all cause neutropenia.
• Rheumatologic Causes: Certain autoimmune disorders, such as rheumatoid arthritis, can also lead to neutropenia.
• Iatrogenic Causes: Medications, such as chemotherapy or immunosuppressive agents, can cause neutropenia as a side effect.

Key Points

• SCN is a rare genetic disorder characterized by low levels of granulocytes in the blood.
• The differential diagnosis of SCN involves ruling out other conditions that may present with similar symptoms.
• Cyclic neutropenia, AML, and myelodysplastic syndrome are all potential differential diagnoses for SCN.

References:

[7] Dec 20, 2022 — Kostmann disease was first described in 1956 as a severe congenital neutropenia characterized by low levels of granulocytes.