CD3gamma deficiency

CD3 gamma deficiency is a rare genetic disorder that affects the immune system. The condition is characterized by a partial arrest of T-cell maturation and moderate immunodeficiency [6]. Patients with CD3 gamma deficiency can have a severe combined immunodeficiency (SCID) phenotype or a milder, non-fatal form of disease [2].

The clinical features of CD3 gamma deficiency can vary in severity, ranging from mild to severe. In some cases, the condition may be asymptomatic, while in others, it can lead to recurrent infections and other complications [7]. The laboratory features of CD3 gamma deficiency include T-cell phenotypic and functional defects, particularly in regulatory T cells (Treg) [8].

CD3 gamma-deficient patients often have a normal number of T cells but with impaired function. This impairment is especially prominent in Treg cells, which play a crucial role in maintaining immune homeostasis [8]. The peripheral T-cell repertoire of CD3 gamma-deficient individuals may also be affected, leading to an altered distribution of T cell subsets [8].

CD3 chain expression defects, including CD3 gamma, epsilon, delta, and zeta chain subunits, are autosomal recessive inherited severe combined immunodeficiency (SCID) disorders. These conditions are characterized by a partial arrest of T-cell maturation and moderate immunodeficiency [9].

CD3 gamma deficiency, also known as CD3G deficiency, is a rare genetic disorder that affects the immune system. Individuals with this condition may exhibit a range of clinical features, which can vary in severity.

Common Signs and Symptoms:

• Recurrent Infections: Patients with CD3 gamma deficiency are prone to recurrent respiratory infections, otitis (ear infections), candidiasis (fungal infections), and other opportunistic infections.
• Autoimmune Disorders: Some individuals may develop autoimmune conditions such as:
  • Autoimmune hemolytic anemia
  • Vitiligo (skin depigmentation)
  • Hashimoto's thyroiditis
  • Autoimmune enteropathy (inflammation of the intestines)
• Gastrointestinal Issues: Patients may experience chronic diarrhea, recurrent gastroenteritis, and abnormal intestine morphology.
• Failure to Thrive: Infants with CD3 gamma deficiency may exhibit failure to thrive due to recurrent infections and gastrointestinal issues.

Other Possible Symptoms:

• Anoperineal fistula (abnormal connection between the anus and perineum)
• Chronic diarrhea
• Recurrent gastroenteritis

It's essential to note that the clinical phenotype of CD3 gamma deficiency can be highly heterogeneous, ranging from asymptomatic to severe recurrent infections in infancy. [1][2][6][8]

References: [1] - Patients with CD3 delta, epsilon, and zeta deficiency have a typical SCID phenotype in infancy (FTT, diarrhea, opportunistic infections). [2] [2] - Clinical features · Abnormal intestine morphology · Anoperineal fistula · Chronic diarrhea · Recurrent gastroenteritis. [3] [6] - CD3G deficiency​​ Individuals with CD3 gamma deficiency have clinical phenotypes ranging from immune deficiency to immune dysregulation with autoimmunity. [7] [8] - by AVM Marin · 2014 · Cited by 12 — Most patients show SCID or CID features such as recurrent respiratory infections, otitis, candidiasis, diarrhea, failure to thrive, and sometimes autoimmune ...

CD3 gamma deficiency is a rare genetic disorder that affects the immune system, making it difficult for the body to fight off infections and diseases. Diagnostic testing for CD3 gamma deficiency involves several steps to confirm the diagnosis.

Genetic Testing Genetic testing is the primary method for diagnosing CD3 gamma deficiency (see [6] and [7]). This test can identify mutations in the CD3G gene, which is responsible for encoding the CD3 gamma subunit. Genetic testing can be performed on blood samples or other tissues.

• Molecular/genetic testing can be pursued either in parallel to the immunological assessment, depending on the clinical phenotype, or sequential to it (see [10]). If a molecular diagnosis is not established at the first attempt, and if the likelihood of a genetic defect is high, recommend an iterative approach, which can also be used when characterizing VUSs.
• Diagnostic testing of this gene is recommended to identify a potential genetic basis for a condition (see [9]). This type of testing can inform prognosis and clinical management.

Immunological Assessment In addition to genetic testing, an immunological assessment is essential to diagnose CD3 gamma deficiency. This involves evaluating the immune system's function and identifying any abnormalities.

• Flow cytometry can be used to assess the number and function of T cells (see [15]). This test can help identify any defects in the CD3 complex.
• Serum protein electrophoresis can also be performed to evaluate the levels of immunoglobulins and other proteins involved in immune function.

Other Diagnostic Tests Other diagnostic tests may be necessary to rule out other conditions that could be causing similar symptoms. These may include:

• Complete Blood Count (CBC): This test measures the number of red and white blood cells, as well as platelets.
• Blood chemistry tests: These tests evaluate the levels of various chemicals in the blood, such as electrolytes and enzymes.

References

[6] Previous symbol(s) and name(s): CD3-GAMMA DEFICIENCY; Immunodeficiency 17; Immunodeficiency 17, CD3 gamma deficient; SCID-LIKE IMMUNODEFICIENCY, T CELL-PARTIAL, B CELL-POSITIVE, ...

[7] NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice.

[9] Diagnostic testing for myositis includes common laboratory tests (CBC, CMP), serologies, imaging studies and muscle biopsy. ... Theuri M, Nairz M, Seifert M, Schroll A, et al. Regulation of iron homeostasis in anemia of chronic disease and iron deficiency ...

[10] Molecular/genetic testing can be pursued either in parallel to the immunological assessment, depending on the clinical phenotype, or sequential to it. If a molecular diagnosis is not established at the first attempt, and if the likelihood of a genetic defect is high, recommend an iterative approach, which can also be used when characterizing VUSs.

[15] Introduction and Outline. Since the topic of primary immunodeficiencies (PIDs) and the associated diagnostic testing is exhaustive and highly complex [], this review article will focus primarily on 2 key methodologies used for the laboratory diagnosis of PIDs - flow cytometry and genetic testing, by offering case-based examples.The hallmark of most PIDs is susceptibility to recurrent and life

CD3gamma deficiency is a rare genetic disorder that affects the immune system, leading to severe combined immunodeficiency (SCID). While there are no specific "drugs" for treating CD3gamma deficiency, treatment typically involves managing symptoms and preventing infections. Here's an overview of the current understanding:

• Hematopoietic Stem Cell Transplantation (HSCT): This is considered a curative treatment option for CD3gamma deficiency [3]. HSCT involves

Differential Diagnosis of CD3gamma Deficiency

CD3gamma deficiency is a rare genetic disorder that affects the immune system, leading to impaired T-cell function and increased susceptibility to infections. When diagnosing this condition, it's essential to consider other potential causes of similar symptoms. Here are some conditions that may be part of the differential diagnosis:

• TCRID (T-Cell Receptor Deficiency): This is a group of rare genetic disorders characterized by impaired T-cell function and increased susceptibility to infections [9]. Patients with TCRID can present with similar clinical features to those with CD3gamma deficiency, including T lymphopenia.
• IL7Rα mutations: Mutations in the IL7Rα gene have been associated with severe combined immunodeficiency (SCID) and impaired T-cell development [8].
• FOXN1 mutations: FOXN1 is a transcription factor essential for thymocyte development. Mutations in this gene can lead to SCID and impaired T-cell function [8].
• Coronin-1A mutations: Coronin-1A is a protein involved in the regulation of T-cell activation and proliferation. Mutations in this gene have been associated with impaired T-cell function and increased susceptibility to infections [9].

Key Features to Consider

When considering these conditions as part of the differential diagnosis, it's essential to note the following key features:

• T lymphopenia: A decrease in the number of T cells can be a common feature among these conditions.
• Impaired T-cell function: All these conditions are characterized by impaired T-cell function, leading to increased susceptibility to infections.
• Genetic mutations: Many of these conditions are associated with genetic mutations that affect T-cell development and function.

Clinical Features

The clinical features of CD3gamma deficiency can vary widely among patients. However, some common features include:

• Recurrent infections: Patients with CD3gamma deficiency may experience recurrent infections, particularly those caused by opportunistic pathogens.
• Gastrointestinal symptoms: Some patients may present with gastrointestinal symptoms, such as diarrhea or abdominal pain.
• Skin rashes: Skin rashes can be a feature of some cases of CD3gamma deficiency.

Laboratory Features

The laboratory features of CD3gamma deficiency include:

• T lymphopenia: A decrease in the number of T cells is a hallmark of this condition.
• Impaired T-cell function: Patients with CD3gamma deficiency may have impaired T-cell function, as measured by flow cytometry or other assays.

Diagnosis and Differential Diagnosis

The diagnosis of CD3gamma deficiency can be challenging due to its rarity and the overlap in clinical features with other conditions. A comprehensive diagnostic workup, including genetic testing and immunological assessments, is essential for accurate diagnosis and differential diagnosis.

References:

[8] HK Dadi ·