Immunodeficiency GM4 deficiency syndrome

By SWA

GM4 deficiency syndrome, or more correctly referred to as IgG4-related disease (IgG4-RD), is not a classic immune deficiency. Instead, it's a systemic immune-mediated disorder that involves the overproduction of a specific type of antibody called IgG4. This condition can affect multiple organs throughout the body.

Key Features:

1. IgG4 Antibodies:

  • IgG4 is a subtype of immunoglobulin G (IgG), which are antibodies that help the body fight off infections.

  • In IgG4-RD, IgG4 levels are abnormally high, which is part of what drives the disease.

2. Fibrosis:

  • The disease often leads to fibrosis, or scarring—this is when connective tissue builds up in organs, which can cause stiffness and impaired function.

3. Tumor-like Lesions:

  • Affected organs can develop mass-like swellings or growths that look like tumors but are not cancerous (they’re benign).

4. Systemic Disease:

  • IgG4-RD is a systemic condition, meaning it can affect multiple organs at the same time, such as:

    • Kidneys

    • Liver

    • Pancreas

    • Eyes

    • Salivary glands

    • Lymph nodes

Difference from Immune Deficiencies:

Primary Immune Deficiencies:

  • These are genetic disorders present from birth.

  • The immune system does not function properly, leading to frequent infections.

  • Examples: CVID (Common Variable Immunodeficiency), X-linked agammaglobulinemia (BTK gene mutation).

Secondary Immune Deficiencies:

  • These are acquired later in life due to other illnesses or treatments.

  • Causes can include:

    • Cancer (e.g., leukemia, lymphoma)

    • Infections (like HIV)

    • Medications (like chemotherapy or immunosuppressants)

    • Malnutrition or chronic diseases

GM4 Deficiency – Is It an Immunodeficiency?

  • The term "GM4 deficiency syndrome" is sometimes confused with immune deficiency, but IgG4-RD is not a true immune deficiency in the usual sense.

  • It is better classified as a dysregulation of the immune system, not a lack of immune function.

Antibody Deficiencies (Hypogammaglobulinemia):

Primary (genetic):

  • Caused by inherited gene mutations that impair B-cell development and antibody production.

  • Examples:

    • CVID

    • Selective IgA deficiency

    • X-linked agammaglobulinemia (BTK gene mutation)

Secondary (acquired):

  • Result from other conditions or treatments, like:

    • HIV/AIDS

    • Cancer (especially blood cancers)

    • Chemotherapy or steroids

    • Organ transplant immunosuppressive therapy

    • Chronic inflammation or malnutrition

Summary:

  • GM4 deficiency syndrome (IgG4-RD) is a chronic immune-mediated disease, not a classical immune deficiency.

  • It causes increased IgG4 production, fibrosis, and benign tumor-like growths in various organs.

  • It is distinct from primary immune deficiencies, which involve weakened immune defense, and from secondary immune deficiencies, which are acquired.

    List of variants in gene BTK reported as likely pathogenic for X-linked agammaglobulinemia

    https://clinvarminer.genetics.utah.edu/variants-by-condition/X-linked%20agammaglobulinemia/gene/BTK/likely%20pathogenic

    © 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right. Library of Congress Card Number: LCN 00-192742

     

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