immunodeficiency 27A

Immunodeficiency 27A (IMD27A) Overview

Immunodeficiency 27A, also known as IMD27A, is a rare genetic disorder caused by autosomal recessive IFNGR1 deficiency. This condition results in impaired interferon-gamma mediated immunity, making patients highly susceptible to severe mycobacterial infections.

Key Features of IMD27A:

• Autosomal Recessive Inheritance: IMD27A is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Impaired Interferon-Gamma Mediated Immunity: Patients with complete IFNGR1 deficiency have impaired interferon-gamma mediated immunity, leading to severe mycobacterial infections.
• Severe Clinical Phenotype: Complete deficiency leads to a severe clinical phenotype, characterized by high circulating levels of IFNG and failure of cellular responses to IFNG.

Clinical Features:

• Abnormality of blood and blood-forming tissues
• Anemia
• Abnormality of metabolism/homeostasis
• Abnormality of the digestive system

Definition and Classification: IMD27A is a primary immunodeficiency disease characterized by high circulating levels of IFNG, failure of cellular responses to IFNG, and susceptibility to severe mycobacterial infections.

References: [1] [2] [3] [4] [5]

Immunodeficiency 27A (IMD27A) is a rare genetic disorder caused by autosomal recessive IFNGR1 deficiency. Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections [2]. This condition can be categorized as a form of Mendelian susceptibility to mycobacterial disease (MSMD).

The signs and symptoms of immunodeficiency 27A may include:

• Frequent and recurrent bacterial and viral infections, including bacteremia, pneumonia, and meningitis
• Severe and often fatal mycobacterial infections
• Inflammation and infection of internal organs
• Recurrent sinus infections, ear infections, and skin infections

It's worth noting that the symptoms can vary from person to person, and not everyone with immunodeficiency 27A will experience all of these symptoms [11]. However, early recognition and treatment are crucial in managing this condition.

References: [2] - Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. [11] - Signs and symptoms differ depending on the type of primary immunodeficiency disorder, and they vary from person to person.

Diagnostic Tests for Immunodeficiency

Immunodeficiency disorders can be challenging to diagnose, but various tests can help confirm the condition. Here are some diagnostic tests used to identify immunodeficiency:

• Blood tests: Blood tests can determine typical levels of infection-fighting proteins (immunoglobulins) in your blood and measure the levels of blood cells and immune system cells [1].
• Complete Blood Count (CBC): A CBC with manual differential is an initial screening test that can detect abnormalities in blood cells characteristic of specific immunodeficiency disorders [3][13].
• Quantitative Immunoglobulin (Ig) measurements: This test measures the levels of immunoglobulins in your blood, which can help diagnose immunodeficiency [1][3].
• Antibody titers: Antibody titers measure the level of antibodies in your blood and can be used to diagnose immunodeficiency [1][3].
• Skin testing for delayed hypersensitivity: This test measures the body's ability to respond to certain substances, which can help diagnose immunodeficiency [3].

Genetic Testing

Genetic testing is also used to diagnose immunodeficiency. There are three main types of genetic testing:

• Panel testing: This type of testing looks for specific mutations in genes that cause immunodeficiency [9].
• Whole Exome Sequencing (WES): WES tests the entire exome, which includes all the protein-coding regions of your genome, to identify mutations causing immunodeficiency [9].
• Whole Genome Sequencing (WGS): WGS tests the entire genome to identify mutations causing immunodeficiency [9].

Other Tests

Other tests may be performed to confirm a diagnosis of immunodeficiency. These include:

• Complement levels in the blood: This test measures the level of complement proteins in your blood, which can help diagnose immunodeficiency [5].
• Flow cytometry: This test measures the number and function of immune cells, which can help diagnose immunodeficiency [8][12].

It's essential to consult with a healthcare professional for an accurate diagnosis and treatment plan.

Treatment Options for Immunodeficiency

Immunodeficiency can be treated using various medications, depending on the underlying cause and severity of the condition. Here are some common drug treatment options:

• Antibiotics: These are used to treat bacterial infections that occur due to immunodeficiency (7). Antibiotics such as amoxicillin and ciprofloxacin are commonly prescribed.
• Anti-fungals: Antifungal medications like fluconazole and itraconazole may be used to treat fungal infections (7).
• Immunoglobulin replacement therapy: This involves administering antibodies to help replace the missing or defective antibodies in the body (5). Immunoglobulins can be administered intravenously (IVIG) or subcutaneously.
• Gene therapy: In some cases, gene therapy may be used to correct the genetic defect causing immunodeficiency. This involves replacing the faulty gene with a healthy one using stem cells from the patient's own body (2).
• Rituximab: This medication has been used to treat associated hemolytic anemia and thrombocytopenia in patients with immunodeficiency (8).

Other Medications

In addition to these primary treatments, other medications may be used to manage symptoms or prevent infections. These include:

• Steroids: Corticosteroids like prednisone and methylprednisolone can be used to suppress the immune system and reduce inflammation.
• Colchicine: This medication is sometimes used to treat gout attacks that occur in patients with immunodeficiency.
• Hydroxychloroquine (Plaquenil): This antimalarial medication has been used to treat autoimmune conditions associated with immunodeficiency.
• Sulfasalazine: This medication may be used to treat inflammatory bowel disease and other autoimmune conditions.

Important Considerations

It's essential to note that individual risks and benefits of treatment should be discussed with a healthcare provider. Additionally, the use of certain medications can have side effects or interact with other medications (4).

Differential Diagnosis of Immunodeficiency 27A

Immunodeficiency 27A (IMD27A), also known as autosomal recessive IFNGR1 deficiency, is a rare genetic disorder characterized by severe susceptibility to mycobacterial infections. When considering the differential diagnosis for IMD27A, several conditions should be taken into account.

• Mendelian Susceptibility to Mycobacterial Disease (MSMD): This condition shares similar clinical features with IMD27A, including severe and often fatal mycobacterial infections. MSMD is caused by mutations in genes involved in the immune response against mycobacteria [1][2].
• Common Variable Immunodeficiency (CVID): Although CVID typically presents with hypogammaglobulinemia and recurrent infections, some cases may exhibit similar clinical features to IMD27A, such as interstitial lung disease and autoimmune cytopenias [10].
• Severe Combined Immunodeficiency (SCID): While SCID is characterized by severe combined T and B cell deficiency, leading to recurrent bacterial infections, it can be distinguished from IMD27A by the presence of malignancies and opportunistic infections in SCID patients [14].

Key Diagnostic Features

To arrive at a diagnosis of IMD27A, clinicians should consider the following key features:

• Early and often fatal mycobacterial infections: This is a hallmark feature of IMD27A, distinguishing it from other immunodeficiencies.
• Autosomal recessive inheritance pattern: Patients with complete IFNGR1 deficiency exhibit a severe clinical phenotype, whereas partial deficiencies may present with milder symptoms [3].
• Genetic testing: Molecular diagnosis can confirm the presence of homozygous or compound heterozygous mutations in the IFNGR1 gene on chromosome 6q23 [13].

Laboratory Evaluation

Initial screening tests for immunodeficiency, including a complete blood count (CBC) with manual differential, quantitative immunoglobulin measurements, and antibody titers, may be necessary to support a diagnosis of IMD27A [11].