Adenosine deaminase 2 deficiency
Adenosine deaminase 2 deficiency | |
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Autosomal recessive pattern is the inheritance manner of this condition | |
Classification and external resources |
Adenosine deaminase 2 deficiency is a vasculitis syndrome.[1][2] It is due to mutations in the ADA2 gene which encodes the adenosine deaminase 2 protein. The clinical features of this condition are protean and it may be easily missed.
Genetics
The ADA2 gene is located in the long arm of chromosome 22 (22q11.1).
Over 60 pathogenic mutations have been recognised in ADA2. In all clinical cases to date both copies of the gene have been mutated implying a recessive inheritance.
Epidemiology
This is a rare condition with less than 200 cases reported.[3]
Clinical features
The age of onset of symptoms is variable: 24% of reported patients present before 1 year of age. 77% present before the age 10 years. Adult onset has also been described. 5-10% die from this disease by the age of 30 years.
Like all vasculitis syndromes the features depend on which is organ is involved. Most commonly the gut, kidney and liver are affected.
It may affect the skin (livedo reticularis and livedo racemosa) or brain (stroke).[4] Polyarteritis nodosa in children is also known to occur.[5]
Other conditions associated with this syndrome include hypogammaglobulinemia, pure red cell aplasia, immune thrombocytopenia and neutropenia.
Differential diagnosis
This includes common variable immunodeficiency,[6] bone marrow failure and idiopathic aplastic anemia.
Pathopysiology
This is not understood. The gene is expressed in myeloid cells and macrophages but its function is not known.
Treatment
Thalidomide, tumour necrosis factor antibodies and in severe cases bone marrow transplantation have been used successfully.[7][3]
History
This condition was first reported in 2014.[8]
References
- ↑ Meyts, Isabelle; Aksentijevich, Ivona (2018-06-27). "Deficiency of Adenosine Deaminase 2 (DADA2): Updates on the Phenotype, Genetics, Pathogenesis, and Treatment". Journal of Clinical Immunology. doi:10.1007/s10875-018-0525-8. ISSN 0271-9142.
- ↑ Giannelou, Angeliki; Zhou, Qing; Kastner, Daniel L. (December 2014). "When less is more: primary immunodeficiency with an autoinflammatory kick". Current Opinion in Allergy and Clinical Immunology. 14 (6): 491–500. doi:10.1097/ACI.0000000000000117. ISSN 1473-6322. PMC 4212813. PMID 25337682.
- 1 2 Hashem, Hasan; Kelly, Susan J.; Ganson, Nancy J.; Hershfield, Michael S. (2017-10-05). "Deficiency of Adenosine Deaminase 2 (DADA2), an Inherited Cause of Polyarteritis Nodosa and a Mimic of Other Systemic Rheumatologic Disorders". Current Rheumatology Reports. 19 (11): 70. doi:10.1007/s11926-017-0699-8. ISSN 1534-6307. PMID 28983775.
- ↑ Nanthapisal, Sira; Murphy, Claire; Omoyinmi, Ebun; Hong, Ying; Standing, Ariane; Berg, Stefan; Ekelund, Maria; Jolles, Stephen; Harper, Lorraine (September 2016). "Deficiency of Adenosine Deaminase Type 2: A Description of Phenotype and Genotype in Fifteen Cases". Arthritis & Rheumatology (Hoboken, N.J.). 68 (9): 2314–2322. doi:10.1002/art.39699. ISSN 2326-5205. PMID 27059682.
- ↑ Caorsi, Roberta; Penco, Federica; Schena, Francesca; Gattorno, Marco (2016-09-08). "Monogenic polyarteritis: the lesson of ADA2 deficiency". Pediatric Rheumatology Online Journal. 14 (1): 51. doi:10.1186/s12969-016-0111-7. ISSN 1546-0096. PMC 5015262. PMID 27609179.
- ↑ Springer JM, Gierer SA, Jiang H, Kleiner D, Deuitch N, Ombrello AK, Grayson PC, Aksentijevich I (2018) Deficiency of adenosine deaminase 2 in adult siblings: Many years of a misdiagnosed disease With severe consequences. Front Immunol 9:1361
- ↑ Caorsi, Roberta; Penco, Federica; Grossi, Alice; Insalaco, Antonella; Omenetti, Alessia; Alessio, Maria; Conti, Giovanni; Marchetti, Federico; Picco, Paolo (October 2017). "ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study". Annals of the Rheumatic Diseases. 76 (10): 1648–1656. doi:10.1136/annrheumdis-2016-210802. ISSN 1468-2060. PMID 28522451.
- ↑ Zhou, Qing; Yang, Dan; Ombrello, Amanda K.; Zavialov, Andrey V.; Toro, Camilo; Zavialov, Anton V.; Stone, Deborah L.; Chae, Jae Jin; Rosenzweig, Sergio D. (2014-03-06). "Early-Onset Stroke and Vasculopathy Associated with Mutations in ADA2". New England Journal of Medicine. 370 (10): 911–920. doi:10.1056/nejmoa1307361. ISSN 0028-4793. PMC 4193683. PMID 24552284.