Reticular dysgenesis
Reticular dysgenesis (RD) is a rare, inherited autosomal recessive disease that results in immunodeficiency.[1] Individuals with RD have mutations in both copies of the AK2 gene.[1] Mutations in this gene lead to absence of AK2 protein.[2] AK2 protein allows hematopoietic stem cells to differentiate and proliferate.[2] Hematopoietic stem cells give rise to blood cells.[2]
Differentiation and proliferation of hematopoietic stem cells require a lot of energy and this energy is supplied by the mitochondria.[2] The energy metabolism of mitochondria is regulated by the AK2 protein.[2] If there is a mutation in the protein, that means that the mitochondria metabolism most likely will be altered and will not be able to provide enough energy to the hematopoietic stem cells.[2] As a result, hematopoietic stem cells will not be able to differentiate or proliferate.[2]
The immune system consists of specialized cells that work together to fight off bacteria, fungi and viruses.[3] These cells include T lymphocytes (T cells), that primarily mediate the immune system, B lymphocytes (B cells) and Natural Killer cells.[3] Patients with RD have a genetic defect that affects the T cells and at least one other type of immune cell.[4] Since more than one type of immune cell is affected, this disease is classified as a severe combined immunodeficiency disease (SCID).[3] A weakened immune system leaves patients susceptible to different kinds of infection. Commonly, patients who are diagnosed with RD also have bacterial sepsis and/or pneumonia.[4]The annual incidence has been estimated at 1/3,000,000-1/5,000,000 and both females and males are affected.[5]
Signs and symptoms[edit | edit source]
| Signs and Symptoms | Approximate Number of Patients Affected |
|---|---|
| Abnormality of mitochondria metabolism | 90% |
| Abnormality of Neutrophils | 90% |
| Anemia | 90% |
| Aplasia/Hypoplasia of the thymus | 90% |
| Cellular immunodeficiency | 90% |
| Decreased antibody level in blood | 90% |
| Diarrhea | 90% |
| Hearing Impairment | 90% |
| Recurrent respiratory infection | 90% |
| Sepsis | 90% |
| Abnormality of temperature regulation | 50% |
| Malabsorption | 50% |
| Weight Loss | 50% |
| Dehydration | 7.5% |
| Skin rash | 7.5% |
| Skin Ulcer | 7.5% |
Risk factors[edit | edit source]
- Condition follows an autosomal recessive pattern[7]
Diagnosis[edit | edit source]
Health professionals must look at a person's history, symptoms, physical exam and laboratory test in order to make a diagnosis. If the results show patients with low levels of lymphocytes, absence of granulocytes or absence of thymus then the patient may be suspected to have RD.[4]
Treatment[edit | edit source]
RD can only be treated temporarily through Hematopoietic stem cell transplantation (HSCT) and Cytokine Therapy.[4][8][9]
Hematopoietic Stem Cell Transplantation[edit | edit source]
Transplantation of stem cells are taken from the bone marrow, peripheral blood or umbilical cord of healthy, matched donors.[10] Hematopoietic Stem Cell Transplantation (HSCT) involves intravenous infusion of stem cells to those who have either a damaged bone marrow or defective immune system.[4][10] Transplantation is a simple process. Bone marrow product is infused through a central vein over a period of several hours.[10] The hematopoietic cells are able to go to the bone marrow through tracking mechanisms.[10] Patients who suffer from RD will now have more stem cells that can differentiate into immune cells.
Cytokine Therapy[edit | edit source]
Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) can be used as a temporary cure.[8] GM-CSF stimulates production of white blood cells.[8] This cure is commonly used in patients who are awaiting bone marrow transplantation.[8] Response to this cure can vary.[8] Those with a more severe combined immunodeficiency may have no response to this therapy.[8]
Prognosis[edit | edit source]
The survival range is estimated to be 3 days to 17 weeks without treatment.[8] Patients die due to bacterial or viral infections.[8] Aggressive treatment with antibiotics is required and bone marrow transplant is common.[8] Patients undergoing bone marrow transplant, specifically from a matched sibling, have a higher 5 year survival rate than those receiving a transplant from other donors.[10]
Research[edit | edit source]
Gene Therapy[edit | edit source]
Gene therapy is a relatively new concept in the field of SCID.[11] This therapy is currently undergoing clinical trial and has cured a small number of children suffering from X-linked SCID and recessive allele SCID.[11] Gene therapy aims to correct the underlying genetic abnormality in SCID.[11] In the case of RD, the genetic abnormality would be AK2 malfunction.[2] Stem cells are taken from an affected child's blood or bone marrow.[11] Then in laboratory conditions the stem cells are manipulated and corrected with gene technology.[11] They are then injected back into the patient.[11] Similarly, in bone transplant, stem cells are able to find their way back through tracking mechanisms.[10][11]
References[edit | edit source]
- ↑ 1.0 1.1
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7
- ↑ 3.0 3.1 3.2 "The Immune System and Primary Immunodeficiency | Immune Deficiency Foundation". primaryimmune.org. Retrieved 2016-11-20.
- ↑ 4.0 4.1 4.2 4.3 4.4
- ↑ "Reticular dysgenesis: epidemiology". rarediseases. Genetic and rare diseases information center. Retrieved 17 April 2018.
- ↑ "Reticular dysgenesis". GARD.
- ↑ 7.0 7.1 7.2
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 8.7 8.8
- ↑
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5
- ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6
External links[edit | edit source]
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|---|---|
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