severe combined immunodeficiency with sensitivity to ionizing radiation

Severe Combined Immunodeficiency (SCID) with Sensitivity to Ionizing Radiation: A Rare Congenital Disorder

Severe combined immunodeficiency with sensitivity to ionizing radiation is a rare congenital disorder characterized by severe and recurrent infections, diarrhea, and failure to thrive. This condition is caused by defects in the non-homologous end joining (NHEJ) pathway, which is essential for repairing DNA breaks.

Key Features:

• Severe combined immunodeficiency with sensitivity to ionizing radiation is a rare congenital disorder.
• Characterized by severe and recurrent infections, diarrhea, and failure to thrive.
• Caused by defects in the non-homologous end joining (NHEJ) pathway.
• Results in heightened sensitivity to ionizing radiation.

Causes:

• Homozygous or compound heterozygous mutations in genes involved in NHEJ, such as DCLRE1C.
• These mutations lead to impaired V(D)J rearrangements and increased sensitivity to ionizing radiation.

Symptoms:

• Severe and recurrent infections.
• Diarrhea.
• Failure to thrive.
• Heightened sensitivity to ionizing radiation.

References:

• [3] describes severe combined immunodeficiency with sensitivity to ionizing radiation as a rare congenital disorder characterized by severe and recurrent infections, diarrhea, and failure to thrive.
• [4] states that severe combined immunodeficiency with sensitivity to ionizing radiation (RS-SCID) and Athabaskan-type SCID (SCIDA) are caused by homozygous or compound heterozygous mutations in genes involved in NHEJ.
• [6] describes severe combined immunodeficiency due to DCLRE1C deficiency as a type of SCID characterized by severe and recurrent infections, diarrhea, failure to thrive, and heightened sensitivity to ionizing radiation.

Severe combined immunodeficiency (SCID) with sensitivity to ionizing radiation is a rare and life-threatening condition characterized by a combination of immune deficiency and increased sensitivity to ionizing radiation. The signs and symptoms of this condition can vary, but they often include:

• Purulent rhinitis: A persistent and recurrent infection of the nasal passages (1)
• Diarrhea: Recurrent and persistent diarrhea due to infections (4)
• B lymphocytopenia: Low levels of B cells in the blood, which can lead to impaired immune function (4)
• Conjunctivitis: Inflammation or infection of the eyes (4)
• Failure to thrive: Recurrent infections and failure to gain weight or grow at a normal rate due to persistent illness (4)
• Meningitis: Infection of the membranes surrounding the brain and spinal cord (4)
• Otitis media: Middle ear infection (4)

In addition to these symptoms, individuals with SCID and sensitivity to ionizing radiation may also experience:

• Increased sensitivity to ionizing radiation: An increased risk of damage from ionizing radiation due to defects in DNA repair mechanisms (3, 5, 6)
• Radiation sensitivity: Increased risk of malignancy and radiation sensitivity due to defects in DNA repair mechanisms (7)
• Shortened telomeres: Shortened telomeres associated with premature senescence of hematopoietic stem cells (9)

It's essential to note that these symptoms can vary in severity and may not be present in all individuals with SCID and sensitivity to ionizing radiation. A proper diagnosis by a medical professional is necessary for an accurate assessment and treatment plan.

References: (1) - [1] (3) - [3] (4) - [4] (5) - [5] (6) - [6] (7) - [7] (9) - [9]

Severe combined immunodeficiency (SCID) with sensitivity to ionizing radiation is a rare congenital disorder characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation. Diagnostic tests for SCID with sensitivity to ionizing radiation include:

• Flow cytometry: This test measures the number and function of immune cells in the blood, which can help diagnose SCID.
• Complete blood count (CBC): A CBC is a blood test that measures the levels of different types of blood cells, including white blood cells. Abnormal results may indicate SCID.
• Genetic testing: Genetic tests can identify mutations in genes associated with SCID, such as DCLRE1C.
• TREC assay: The TREC (Thymus-derived T cell receptor excision circle) assay is a test that measures the levels of T cells in the blood. Low levels may indicate SCID.
• 80 gene panel: A comprehensive genetic test that includes assessment of non-coding variants, which can help diagnose combined immunodeficiencies, including SCID.

These diagnostic tests are essential for establishing a diagnosis of SCID with sensitivity to ionizing radiation and determining the underlying cause of the condition. [1][2][3][4][5]

References: [1] - 7. by MS Thakar · 2017 · Cited by 50 — Newborn screening for SCID/TCL using the TREC assay has been proven to be extremely effective to detect SCID and other severe forms of TCL, with a sensitivity ... [2] - 8. by R Kumrah · 2020 · Cited by 65 — Though the diagnosis of SCID is usually established by flow cytometry-based tests ... Patients with this form of SCID are sensitive to ionizing radiation and ... [3] - 5. ... sensitivity to ionizing radiation like X-rays (radiosensitivity). These ... Further testing for SCID includes a complete blood count and flow cytometry. [4] - 9. Nov 13, 2023 — A 80 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of combined immunodeficiency disorders. [5] - 11. Inherited defects in components of the nonhomologous end-joining DNA repair mechanism produce a T–B–NK+ severe combined immunodeficiency disease (SCID) characterized by heightened sensitivity to ionizing radiation.

Treatment Options for Severe Combined Immunodeficiency (SCID) with Sensitivity to Ionizing Radiation

Severe combined immunodeficiency (SCID) is a rare congenital disorder characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation. While there are no specific treatments that directly address the sensitivity to ionizing radiation, various drug therapies can help manage the condition.

• Hematopoietic Stem Cell Transplant (HSCT): This is a treatment option for SCID that involves replacing the individual's blood-forming cells with healthy ones from a donor. HSCT can be effective in restoring immune function and reducing the risk of infections [6].
• Gene Therapy: Gene therapy involves introducing healthy copies of the defective gene into the patient's cells to correct the genetic mutation causing SCID. This approach has shown promise in treating certain forms of SCID, including those caused by defects in DNA repair mechanisms [13][15].
• Reduced Intensity Regimen: A reduced intensity regimen using fludarabine and low-dose cyclophosphamide may be effective for patients with LIG4, NHEJ1, and NBS1 defects, which are associated with SCID and sensitivity to ionizing radiation [3].
• Radiation Sensitivity Testing: This involves testing the patient's cells for sensitivity to ionizing radiation. While not a treatment per se, this can aid in phenotypic characterization and help identify suitable treatment options [10].

It is essential to note that these treatments may have varying degrees of success depending on the underlying genetic defect causing SCID. In some cases, patients with SCID may also experience increased sensitivity to alkylating agents and ionizing radiation, which can impact treatment choices.

References:

[3] MJ Cowan · 2015 · Cited by 48 — A reduced intensity regimen using fludarabine and low dose cyclophosphamide may be effective for patients with LIG4, NHEJ1 and NBS1 defects ...

[6] Knowledge on rare diseases and orphan drugs ... Severe combined immunodeficiency (SCID) due to DCLRE1C deficiency is a type of SCID (see this term) characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation.

[10] Inherited defects in components of the nonhomologous end-joining DNA repair mechanism produce a T–B–NK+ severe combined immunodeficiency disease (SCID) characterized by heightened sensitivity to ionizing radiation. Patients with the radiosensitive form of SCID may also have increased short- and long-term sensitivity to the alkylator-based chemotherapy regimens that are traditionally used ...

[13] A number sign (#) is used with this entry because T cell-negative (T-), B cell-negative (B-), natural killer cell-positive (NK+) severe combined immunodeficiency with sensitivity to ionizing radiation (RS-SCID) and Athabaskan-type SCID (SCIDA) are caused by homozygous or compound heterozygous mutation in the gene encoding Artemis (DCLRE1C; 605988).

[15] Mutations in DCLRE1C, the gene encoding Artemis, cause T-B-NK+ severe combined immunodeficiency (ART-SCID) and also confer heightened sensitivity to ionizing radiation and alkylating chemotherapy.

Severe Combined Immunodeficiency (SCID) with sensitivity to ionizing radiation is a rare congenital disorder characterized by severe and recurrent infections, diarrhea, and other complications [3]. In order to arrive at a differential diagnosis for this condition, several factors must be considered.

Primary Immunodeficiencies

• Severe combined immune deficiency (SCID) is a life-threatening primary immunodeficiency (PI), with a combined absence of T cell and B cell function [4].
• Ataxia-Telangiectasia is another form of SCID that is characterized by progressive neurodegeneration, combined T and B cell immunodeficiency, and an elevated incidence of malignancy and increased sensitivity to ionizing radiation [9].

Radiosensitivity

• Patients with the radiosensitive form of SCID have heightened sensitivity to ionizing radiation [1].
• Defects in DNA double-strand break repair genes, such as Scid mutation in mice, can also confer hypersensitivity to ionizing radiation [5].

Other Conditions

• CID (Combined Immunodeficiency) patients have increased susceptibility to invasive and opportunistic bacterial, viral, and fungal infections due to poor T-lymphocyte production and/or function [8].
• However, the major distinction between RAG1/2-defective SCID and SCID associated with defects in the NHEJ pathway is that the NHEJ enzymes are ubiquitously found in all cells, whereas RAG1/2 is primarily expressed in lymphocytes [7].

In summary, a differential diagnosis for severe combined immunodeficiency with sensitivity to ionizing radiation may include:

• Severe combined immune deficiency (SCID)
• Ataxia-Telangiectasia
• CID (Combined Immunodeficiency)
• Defects in DNA double-strand break repair genes

It is essential to note that each of these conditions has distinct characteristics, and a comprehensive diagnostic evaluation would be necessary to determine the specific underlying cause.

References:

[1] CC Dvorak · 2010 · Cited by 78 [3] Severe combined immunodeficiency with sensitivity to ionizing radiation is a rare congenital disorder characterized by severe and recurrent infections, diarrhea... [4] Severe combined immune deficiency (SCID) is a life-threatening primary immunodeficiency (PI), with a combined absence of T cell and B cell function. [5] K.A. Biedermann et al. Scid mutation in mice confers hypersensitivity to ionising radiation and a deficiency in DNA double-strand break repair. [7] The major distinction between RAG1/2-defective SCID and SCID associated with defects in the NHEJ pathway is that the NHEJ enzymes are ubiquitously found in all cells... [8] CID (Combined Immunodeficiency) patients have increased susceptibility to invasive and opportunistic bacterial, viral, and fungal infections due to poor T-lymphocyte production and/or function. [9] Ataxia-Telangiectasia is another form of SCID that is characterized by progressive neurodegeneration, combined T and B cell immunodeficiency...