![]() ![]() Symptoms include impaired kidney function, gouty arthritis, and self-mutilating behaviors regularly leading to tissue loss, including repeated lip/finger/hand biting, head banging, and face scratching. Lesch-Nyhan syndrome is a rare X-linked genetic disorder that most often affects males. #adenosinedeaminase #ADAdeficiency #purinesalvagepathway #inheriteddiseases #SCID #severecombinedimmunodeficiency #genetherapy #geneticdisorders #geneticdiseases #heriditarydisorders #heriditarydiseases #immunopathologyĪdenosine Deaminase (ADA)–Deficient Severe Combined Immune Deficiency (SCID) in the US Immunodeficiency Network (USIDNet) Registry These modified blood-forming stem cells are then transplanted back into the patient, where more of them are naturally replicated by the body, ultimately alleviating the symptoms caused by the ADA gene mutation. A sample of stem cells is typically taken from the patient’s bone marrow and then genetically modified by inserting a functional copy of the ADA gene into each stem cell’s genetic code (Aiuti, Roncarolo, & Naldini, 2017 Aiuti et al., 2009). Clinical trials have demonstrated gene therapy’s ability to restore normal purine metabolism and subsequent immune functions (Aiuti et al., 2017 Aiuti et al., 2009). Recent research has demonstrated that gene therapy is effective when using a hematopoietic or blood-forming stem cell transplant (HSCT) instead of risking complications of a bone marrow transplant (Aiuti et al., 2017 Aiuti et al., 2009). ADA deficiency can present in infancy, childhood, adolescence, or adulthood, and presenting symptoms include common signs of infection, such as pneumonia, widespread skin rashes, and or chronic gastrointestinal issues (Adenosine deaminase deficiency, NIH & MedlinePlus). While a mutation of the ADA gene is a central cause of the deficiency, age of onset and severity are linked to approximately thirty different genotypes (Adenosine deaminase deficiency, NIH & MedlinePlus Arredondo-Vega FX et al., 1998). Affected children grow much slower than their peers, and cognitive developmental delays have been observed (Adenosine deaminase deficiency, NIH & MedlinePlus). However, ADA deficiency affects more than just the immune system. Inosine is necessary for forming some DNA synthesis precursor molecules, so low levels lead to subpar expression of DNA necessary for white blood cell formation and proper immune responses (USMLE, 2023). Thus, ADA deficiency leads to abnormally high concentrations of deoxy-adenosine/adenosine (toxic to white blood cells) but also very low levels of inosine, which is even more problematic (Adenosine deaminase deficiency, NIH & MedlinePlus USMLE, 2023 USMLE, 2023). The purine salvage pathway recycles used purine bases into new purine nucleotides for DNA synthesis (Sauer et al., 2012 USMLE, 2023). Adenosine Deaminase (ADA) Deficiency is an inherited mutation of the ADA gene responsible for causing approximately 10-15% of Severe Combined Immunodeficiency (SCID) diagnoses (a group of inherited disorders that make people unable to fight against infections) (see previous post for more info on SCID) (GARD, NIH Kuo et al., 2020).ĪDA is an enzyme in the purine salvage pathway used to degrade deoxy-adenosine/adenosine (toxic DNA degradation byproducts) into deoxy-inosine/inosine (non-toxic) (ADA gene, MedlinePlus Adenosine deaminase deficiency, NIH & MedlinePlus). ![]()
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