One of the rarest and most severe forms of ☞Severe Combined Immunodeficiency Syndrome (SCIDS) characterized by sensorineural deafness, agranulocytosis, lymphopenia, and lymphoid and thymic hypoplasia with absent cellular and humoral immunity functions. Prognosis is generally poor in the first weeks of life.
Reticular Dysgenesis; De Vaal Disease; Congenital Aleukia; Severe Combined Immunodeficiency with Leukopenia; Hematopoietic Hypoplasia Syndrome.
First described by O. M. de Vaal and V. Seynhaeve in 1959.
Mutations in the AK2 gene (1p35.1) are responsible for reticular dysgenesia. The AK2 enzyme is located in the mitochondrial intermembrane space and reversibly catalyzes the transfer of a phosphate group from an ATP to an AMP resulting in the production of two ADP molecules. The AK2 enzyme also co-controls mitochondrial reactive oxygen species and regulates cell survival.
Blood cell count shows normal erythrocytes and platelets, but no leukocytes. Bone marrow shows absent myeloid elements; myeloid lineage has a characteristic maturation arrest at the stage of promyelocyte. Thymus is small and without Hassall corpuscles. Lymph nodes and spleen are hypoplastic and histologically devoid of lymphocytes. The sensorineural deafness is an obligatory clinical feature.
Nearly all affected cases died from overwhelming infections within a few days or weeks of birth. One child survived for 17 weeks in an isolated sterile environment. One case was reported to have bone marrow transplant from an HLA-identical brother and survived with full hematological and immunological reconstitution to 3 years of age. Hematopoietic stem cell transplantation is currently the only option to correct the immunological and hematological phenotype.
Precautions before anesthesia
Maintain sterility in all procedures. These individuals should be isolated at all time.
No known experience because of the severity and the very early mortality associated with this condition. Anesthetic considerations are related to a very high risk of infections.
Prophylactic antibiotics as indicated for immunodeficient patients.
V: Reticular dysgenesia. Lancet II:1123, 1959.
K: Recent advances in understanding the pathogenesis and management of reticular dysgenesis. Br J Haematol
K: Successful bone-marrow transplantation for reticular dysgenesis. Lancet I:671, 1983.