Reticular Dysgenesis (RD) is a rare autosomal recessive immunodeficiency, characterized by the combination of Severe-Combined-Immunodeficiency(SCID) with agranulocytosis and sensorineural deafness. Discovered in 2009, RD is caused by a mutation in the gene encoding adenylate-kinase-2(AK2). In this paper we describe a novel AK2 mutation in a newborn female presenting SCID and RD.
RH was born in January 2019 at 37+6 weeks from an apparently non-consanguineous family. She presented normal APGAR but low-birth-weight, severe leucopenia, hypoglycemia, and abnormal immunology tests (Table 1-2). She failed neonatal hearing test and in her 4th day of life, she was diagnosed with sepsis due to omphalitis.
A bone marrow aspirate was in keeping with severe congenital neutropenia (Table 3), whereas AK2 DNA-sequencing showed a homozygous mutation for the variant c.308G>C, causing a missense change p.(Arg103Pro) at the protein level with deleterious in silico predictions. The RD diagnosis was confirmed, and urgent bone-marrow transplantion has been undertaken.
RD accounts for <2% of all SCID cases, with an annual incidence estimated at 1/3,000,000-1/5,000,000, higher in consanguineous families [2,3]. Mutations in the AK2 gene, located on 1p35.1, are responsible for RD. Until now, AK2 mutations were found in 30 patients from 27 mainly consanguineous families . The variant described has not been reported in the literature and it is absent from the gnomAD population database, although the p.(Arg103Trp) variant has been reported.
The only effective treatment for RD is bone marrow transplant with an overall reported survival of about 68%.