immunodeficiency 31C

Immunodeficiency 31C (IMD31C) Description

Immunodeficiency 31C, also known as IMD31C, is an autosomal dominant disorder characterized by highly variable manifestations of immunologic dysregulation. This condition is caused by gain-of-function mutations in the STAT1 gene.

Key Features:

• Chronic Mucocutaneous Candidiasis (CMC): Most patients present with chronic mucocutaneous candidiasis, a fungal infection that affects the skin and mucous membranes, typically in infancy or early childhood.
• Recurrent Infections: Other highly variable features include recurrent bacterial, viral, fungal, and mycoplasmal infections.

Additional Information:

• Immunodeficiency 31C is an autosomal dominant disorder, meaning a single copy of the mutated gene is sufficient to cause the condition.
• The condition presents with highly variable manifestations, making diagnosis and management challenging.
• Increased IFNG activation is also associated with this condition.

References:

• [1] - Immunodeficiency-31C is caused by heterozygous gain-of-function mutation in the STAT1 gene on chromosome 2q32. (Source: #1)
• [4] - Most patients present in infancy or early childhood with chronic mucocutaneous candidiasis. (Source: #4)
• [5] - A primary immunodeficiency disease characterized by onset in infancy or childhood of chronic mucocutaneous candidiasis and increased IFNG activation. (Source: #5)
• [12] - IMD31C is a disorder of immunologic dysregulation with highly variable manifestations resulting from autosomal dominant gain-of-function mutations in STAT1. (Source: #12)

Immunodeficiency 31C, also known as autosomal dominant gain-of-function mutations in STAT1, presents with a highly variable range of manifestations.

Common features include:

• Recurrent bacterial, viral, fungal, and mycoplasmal infections [2]
• Disseminated dimorphic fungal infections [3]
• Enteropathy (inflammation and infection of the intestines) [3]
• Respiratory infections [4]

Additional features may include: * Osteopenia (low bone density) [5] * Delayed puberty [5] * Intracranial aneurysms (bulging blood vessels in the brain) [5] * Recurrent fever and myalgia (muscle pain) [7] * Lesions resembling polyarteritis nodosa (inflammation of blood vessels) [7] * Livedo (discoloration of the skin due to poor circulation) [7] * Hematological manifestations (abnormalities in the blood cells) [7]

It's essential to note that signs and symptoms can vary greatly from person to person, even within the same family.

References: [1] - This combination of signs and symptoms caused by STAT1 gene mutations is sometimes called immunodeficiency 31C. [2] - These disorder clinical manifestations include primarily respiratory infections, immunodeficiency, and recurring infections with bacteria and other pathogens [3] - Other highly variable features include recurrent bacterial, viral, fungal, and mycoplasmal infections, disseminated dimorphic fungal infections, enteropathy ... [4] - by L Liu · 2022 · Cited by 1 — These disorder clinical manifestations include primarily respiratory infections, immunodeficiency, and recurring infections with bacteria and other pathogens (5 ... [5] - A subset of patients show apparently nonimmunologic features, including osteopenia, delayed puberty, and intracranial aneurysms. [7] - by M Shiraki · 2021 · Cited by 7 — Recurrent fever, myalgia, lesions resembling polyarteritis nodosa, livedo, immunodeficiency and hematological manifestations are also described.

Diagnostic Tests for Immunodeficiency

Immunodeficiency disorders can be diagnosed through various tests that measure the levels and function of different components of the immune system. Here are some common diagnostic tests used to diagnose immunodeficiency:

• Blood tests: Blood tests can determine if you have typical levels of infection-fighting proteins (immunoglobulins) in your blood and measure the levels of blood cells and immune system cells [1]. These tests can also detect abnormalities in blood cells that are characteristic of specific immunodeficiency disorders [12].
• Complete Blood Count (CBC): A CBC is a blood test that measures the levels of different types of blood cells, including white blood cells, red blood cells, and platelets. It can help diagnose conditions such as anemia, infection, or bleeding disorders [3].
• Quantitative immunoglobulin (Ig) measurements: This test measures the levels of specific antibodies in your blood, which can indicate a serious health problem [9].
• Antibody titers: Antibody titers measure the level of antibodies in your blood that are directed against specific antigens. Low antibody titers can indicate immunodeficiency [3].
• Skin testing for delayed hypersensitivity: This test measures the body's ability to respond to certain substances, such as allergens or bacteria [3].
• Genetic testing: Genetic testing can identify known mutations causing various types of primary immunodeficiency (PI) [2]. This test is particularly useful in diagnosing PI.
• Complement levels in the blood: Complement levels in the blood can help diagnose complement deficiencies, which are a type of immunodeficiency disorder [6].
• CD4 T cell count: Monitoring the number of CD4 T cells can help diagnose and manage HIV/AIDS, which is a type of immunodeficiency disorder [8].

These tests can be used to confirm a diagnosis of immunodeficiency and identify the specific type of immunodeficiency disorder. It's essential to note that a combination of clinical findings, laboratory tests, and genetic testing may be necessary to make an accurate diagnosis.

References:

[1] Context 1 [2] Context 2 [3] Context 3 [6] Context 6 [8] Context 8 [9] Context 9 [12] Context 12

Treatment Options for Immunodeficiency

Immunodeficiency can be treated through various methods, including drug therapy, gene therapy, and transplantation.

• Drugs: Medications such as antibiotics, anti-fungals, and corticosteroids are commonly used to treat recurrent infections associated with immunodeficiency [7][9]. Additionally, drugs like rapamycin have been suggested for treatment, although further evaluation is needed [8].
• Gene Therapy: This type of treatment involves correcting the gene responsible for the immunodeficiency using stem cells from the individual. Gene therapy has shown promise in treating primary immunodeficiencies without the need for a donor match [2].
• Transplantation: In some cases, transplantation may be necessary to replace the faulty immune system with a healthy one.

Medications Used in Immunodeficiency Treatment

Several medications are used to treat immunodeficiency, including:

• Immunoglobulin Replacement Therapy (IGRT): This involves replacing antibodies that are deficient or absent in individuals with primary immunodeficiencies [5].
• Rituximab: This medication has been used to treat associated hemolytic anemia and other complications of immunodeficiency [8].

Importance of Individualized Treatment

As with any treatment, individual risks and benefits should be discussed with a healthcare provider. The choice of treatment depends on the specific type and severity of immunodeficiency, as well as the individual's overall health.

References:

[2] This type of treatment involves taking stem cells from the person with primary immunodeficiency, correcting the gene in the cells and then returning the corrected stem cells back to the person via an intravenous infusion. With gene therapy, there is no need to find a suitable donor, as the person's own cells are used.

[5] Immunoglobulin derived from human plasma was first introduced as a treatment option in 1952 when it was injected intramuscularly (IM) to treat people with recurrent infections who had antibody deficiencies.

[7] The treatments most used for the recurrent infections that occur in primary and secondary immunodeficiency are antibiotics, anti-fungals, and in some cases corticosteroids.

[8] Treatment with rapamycin has been suggested, but this therapy awaits proper evaluation. Rituximab has been used to treat associated hemolytic anemia.

[9] Corticosteroids; Medicines used to treat health problems such as rheumatoid arthritis, inflammatory bowel disease, and certain skin conditions.

Immunodeficiency Differential Diagnosis

Immunodeficiency disorders can be challenging to diagnose, and a differential diagnosis approach is often necessary to rule out other conditions that may present with similar symptoms.

Common Conditions in the Differential Diagnosis of Immunodeficiency:

• Bacterial infections: Pneumonia, meningitis, otitis, diarrhea, urinary sepsis, septicemia [1]
• Autoimmune disorders: Such as rheumatoid arthritis, lupus, and Hashimoto's thyroiditis [4]
• Cancer: Including lymphoma, leukemia, and solid tumors [4]
• Infectious diseases: Such as tuberculosis, fungal infections, and viral infections like HIV/AIDS [1]

Laboratory Tests to Confirm Immunodeficiency Diagnosis:

To confirm a diagnosis of immunodeficiency, the following laboratory tests are often performed:

• Complete blood count (CBC) with manual differential
• Quantitative immunoglobulin (Ig) measurements
• Antibody titers
• Skin testing for delayed hypersensitivity [2]

Primary Immunodeficiency Disorders:

Primary immunodeficiency disorders (PIDDs) are a group of rare genetic disorders that impair the immune system's ability to fight infections. PIDDs can be caused by defects in T or B lymphocytes, or both.

Differential Diagnosis of Primary Immunodeficiency:

When diagnosing primary immunodeficiency, it is essential to rule out other conditions that may present with similar symptoms. These include:

• Agammaglobulinemia: A rare genetic disorder characterized by the absence of antibodies [6]
• Atopic dermatitis: A skin condition that can be associated with immunodeficiency [6]
• Cartilage-Hair Hypoplasia: A rare genetic disorder that affects cartilage and hair growth [6]

References:

[1] Context 1 [2] Context 2 [4] Context 4 [6] Context 6