immunodeficiency 19

Immunodeficiency 19 (IMD19): A Severe Combined Immunodeficiency Disorder

Immunodeficiency 19, also known as IMD19, is a rare and severe form of combined immunodeficiency disorder. It is characterized by the onset of recurrent bacterial, viral, and fungal infections in early infancy.

Key Features:

• Autosomal Recessive Inheritance: IMD19 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.
• T Cell-Negative, B Cell-Positive Phenotype: Individuals with IMD19 have a T cell-negative, B cell-positive immune cell phenotype, indicating a significant impairment in their T cell function.
• Recurrent Infections: Patients with IMD19 experience recurrent infections, including bacterial, viral, and fungal infections, which can lead to chronic diarrhea, respiratory problems, and failure to thrive.

Causes and Genetics:

IMD19 is caused by mutations in the CD3D gene located on chromosome 11q23.3. This genetic mutation leads to a severe impairment of T cell function, making it difficult for the body to fight off infections.

Prevalence and Diagnosis:

The exact prevalence of IMD19 is unknown, but it is considered a rare condition. Diagnosis is typically made through immunologic work-up, which shows a T cell-negative, B cell-positive phenotype.

Treatment and Management:

While there is no specific treatment for IMD19, management focuses on preventing infections through good hygiene practices, avoiding live vaccines, and using antibiotics as needed. In some cases, stem cell transplantation may be considered to restore immune function.

References:

• [1] (IMD19) is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype. [1]
• [3] Immunodeficiency 19 is a severe combined immunodeficiency disease that manifests in early infancy with recurrent bacterial, viral, and fungal infections. It is characterized by a T cell-negative, B cell-positive, natural killer cell-positive immune cell phenotype. The disease is caused by mutations in the CD3D gene located on chromosome 11q23.3. [3]
• [14] Immunodeficiency-19 (IMD19) is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T cell-negative, B cell-positive... [14]

Common Signs and Symptoms of Immunodeficiency

Immunodeficiency disorders can manifest in various ways, making it essential to recognize the signs and symptoms early on. Here are some common indicators:

• Frequent Infections: People with immunodeficiency often experience recurring infections, such as:
  • Ear infections (more than 2 within a year) [4][7]
  • Sinus infections (more than 2 within a year, in the absence of allergies) [4][8]
  • Pneumonia (more than 1 per year for over 1 year) [12]
• Inflammation and Infections: Immunodeficiency can lead to inflammation and infection of internal organs, such as:
  • Meningitis
  • Skin infections
  • Thrush (a fungal infection of the mouth or skin)
• Other Symptoms: Additional signs and symptoms may include:
  • Fatigue [11]
  • Swollen spleen, liver, or lymph nodes (splenomegaly, hepatomegaly, or lymphadenopathy) [6]
  • Inflammation of internal organs
  • Chronic diarrhea with weight loss

It's essential to note that these symptoms can vary from person to person and may not be present in everyone with immunodeficiency. If you're experiencing any of these symptoms, consult a doctor for proper evaluation and diagnosis.

References: [4] - Context 4: Signs and symptoms differ depending on the type of primary immunodeficiency disorder... [6] - Context 6: What are the signs of a primary immunodeficiency? · Swollen spleen, liver, or lymph nodes (splenomegaly, hepatomegaly, or lymphadenopathy)... [7] - Context 7: Nov 20, 2020 — The most common signs of immunodeficiency include: Four or more new ear infections within one year; Two or more months on antibiotics with... [8] - Context 8: Signs and symptoms can include: Repeated bouts of pneumonia

Diagnostic Tests for Immunodeficiency

Immunodeficiency 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].
• Complete blood count (CBC): A CBC with manual differential is a common initial screening test for immunodeficiency, which measures the number and types of white blood cells, red blood cells, and platelets [3].
• Quantitative immunoglobulin (Ig) measurements: This test measures the levels of different types of antibodies in your blood, which can indicate a deficiency or excess of these proteins [1].
• Antibody titers: Antibody titers measure the level of antibodies against specific antigens, such as bacteria or viruses. Low antibody titers may indicate immunodeficiency [3].
• Skin testing for delayed hypersensitivity: This test measures your body's ability to respond to certain substances, such as allergens or bacteria, by measuring the skin's reaction to these substances [3].

Genetic Testing

In addition to blood tests and other laboratory tests, genetic testing can also be used to diagnose immunodeficiency. Genetic testing can identify specific mutations in genes that are associated with immunodeficiency [4]. There are three main types of genetic testing used to diagnose PI: panel testing, whole exome sequencing (WES), and whole genome sequencing (WGS) [9].

References

[1] The Immune Deficiency Foundation. Blood tests. [2] The Immune Deficiency Foundation. Peer support program. [3] Initial and Additional Laboratory Tests for Immunodeficiency. [4] Genetic testing for primary immunodeficiency. [5] There are three main ways to test for and diagnose it: laboratory testing, newborn screening, and genetic inheritance / familial history. [6] The best screening test for defects in the classical complement pathway is the total hemolytic complement activity (CH50) assay. [7] We offer a comprehensive range of tests to investigate primary and secondary immune deficiencies. [8] An immunoglobulins test measures the levels of certain antibodies in your blood. Abnormal levels can indicate a serious health problem. [9] Generally, there are three types of genetic testing used to diagnose PI: panel testing, whole exome sequencing (WES), and whole genome sequencing (WGS).

Differential Diagnosis of Immunodeficiency

Immunodeficiency disorders can be challenging to diagnose, as they often present with non-specific symptoms that can mimic other conditions. A differential diagnosis is a process of ruling out other possible causes of a patient's symptoms before arriving at a definitive diagnosis.

Common Differential Diagnoses for Immunodeficiency

1. Bacterial Infections: Pneumonia, meningitis, otitis, diarrhea, urinary sepsis, and septicemia are all potential differential diagnoses for immunodeficiency.
2. Autoimmune Disorders: Conditions such as rheumatoid arthritis, lupus, and Hashimoto's thyroiditis can be mistaken for primary immunodeficiencies.
3. Cancer: Certain types of cancer, like lymphoma or leukemia, can present with symptoms similar to those of immunodeficiency disorders.

Laboratory Tests to Rule Out Differential Diagnoses

1. Complete Blood Count (CBC): A CBC with manual differential can help rule out conditions like anemia, leukopenia, or thrombocytopenia.
2. Quantitative Immunoglobulin Measurements: Measuring IgG, IgM, and IgA levels can help diagnose primary immunodeficiencies.
3. Antibody Titers: Antibody titers can be used to rule out conditions like mononucleosis or toxoplasmosis.

References

• [1] Context 2: Tests are needed to confirm a diagnosis of immunodeficiency (see table Initial and Additional Laboratory Tests for Immunodeficiency).
• [3] Context 3: Common variable immunodeficiency (CVID) is a disorder that involves the following: (1) low levels of most or all of the immunoglobulin (Ig) classes, (2) a lack of B lymphocytes or plasma cells that are capable of producing antibodies, and (3) frequent bacterial infections.
• [10] Context 10: When primary immunodeficiency is suspected, initial laboratory studies include a complete blood cell count (CBC) with manual differential, quantitative immunoglobulin measurements (IgG, IgM, IgA ...
• [12] Context 12: Primary B-cell disorders Common variable immunodeficiency: low IgG and IgA levels, variable IgM levels, usually normal B-cell numbers ...