{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:14:18Z","timestamp":1760235258568,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms22158331","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T08:16:39Z","timestamp":1627978599000},"page":"8331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Germline Mutation of ADA2 Gene in Two \u201cDiscordant\u201d Homozygous Female Twins Affected by Adenosine Deaminase 2 Deficiency: Description of the Bone-Related Phenotype"],"prefix":"10.3390","volume":"22","author":[{"given":"Silvia","family":"Vai","sequence":"first","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4143-1328","authenticated-orcid":false,"given":"Erika","family":"Marin","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4317-0750","authenticated-orcid":false,"given":"Roberta","family":"Cosso","sequence":"additional","affiliation":[{"name":"IRCCS, Istituto Auxologico Italiano, San Giuseppe Hospital, 28824 Verbania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Saettini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universit\u00e0 degli Studi di Milano-Bicocca, Fondazione MBBM, San Gerardo Hospital, 20100 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Bonanomi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universit\u00e0 degli Studi di Milano-Bicocca, Fondazione MBBM, San Gerardo Hospital, 20100 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Cattoni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Universit\u00e0 degli Studi di Milano-Bicocca, Fondazione MBBM, San Gerardo Hospital, 20100 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7594-3300","authenticated-orcid":false,"given":"Iacopo","family":"Chiodini","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy"},{"name":"Department of Medical Biotechnologies and Translational Medicine, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-9581","authenticated-orcid":false,"given":"Luca","family":"Persani","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy"},{"name":"Department of Medical Biotechnologies and Translational Medicine, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6739-4417","authenticated-orcid":false,"given":"Alberto","family":"Falchetti","sequence":"additional","affiliation":[{"name":"Department of Endocrine and Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, 20145 Milan, Italy"},{"name":"IRCCS, Istituto Auxologico Italiano, San Giuseppe Hospital, 28824 Verbania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1056\/NEJMoa1307361","article-title":"Early-onset stroke and vasculopathy associated with mutations in ADA2","volume":"370","author":"Zhou","year":"2014","journal-title":"N. 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