A Novel Germline Mutation of ADA2 Gene in Two “Discordant” Homozygous Female Twins Affected by Adenosine Deaminase 2 Deficiency: Description of the Bone-Related Phenotype

Abstract

Adenosine Deaminase 2 Deficiency (DADA2) syndrome is a rare monogenic disorder prevalently linked to recessive inherited loss of function mutations in the ADA2/CECR1 gene. It consists of an immune systemic disease including autoinflammatory vasculopathies, with a frequent onset at infancy/early childhood age. DADA2 syndrome encompasses pleiotropic manifestations such as stroke, systemic vasculitis, hematologic alterations, and immunodeficiency. Although skeletal abnormalities have been reported in patients with this disease, clear information about skeletal health, with appropriate biochemical-clinical characterization/management, its evolution over time and any appropriate clinical management is still insufficient. In this paper, after a general introduction shortly reviewing the pathophysiology of Ada2 enzymatic protein, its potential role in bone health, we describe a case study of two 27 year-old DADA2 monozygotic female twins exhibiting bone mineral density and bone turnover rate abnormalities over the years of their clinical follow-up.

Adenosine deaminase 2 deficiency in a Chinese patient: Report of one novel mutation and literature review

“…9,20,21 There is no doubt that HSCT is a permanent cure. 22,23 For the time being, our children only found repeated systemic inflammatory reactions, skin manifestations and increased intraocular pressure, no recurrent central system lesions and immune and blood lesions, so it is suitable for the treatment of anti-TNFαdrugs, and the condition is stable and confirm this view.…”

“…Especially those with immune deficiency, cytoreduction, and bone marrow failure phenotype, but the recent reports of B and T lymphocyte abnormal DADA 2 poor response to TNF‐αdrugs, and immunosuppressive agents may increase the risk of infection, thus suggesting the possibility of genotype and phenotype correlation, but further research and development 9,20,21 . There is no doubt that HSCT is a permanent cure 22,23 . For the time being, our children only found repeated systemic inflammatory reactions, skin manifestations and increased intraocular pressure, no recurrent central system lesions and immune and blood lesions, so it is suitable for the treatment of anti‐TNF‐αdrugs, and the condition is stable and confirm this view.…”