Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency
Case presentationA girl aged 2 years and 5 months presented to the hospital with chief complaints of intermittent fever and weakness of the left limb for more than 1 month. The child had transient urticaria appearing on her face for 5 days. The inflammatory biomarkers were significantly increased. B...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1478581/full |
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| author | Haishao Yu Haishao Yu Shuangzhu Lin Lin Li Jiayi Li Qiandui Chen Yuheng Wu Yangfan Qi Wanqi Wang Xingzhi Chang Jie Zhang |
| author_facet | Haishao Yu Haishao Yu Shuangzhu Lin Lin Li Jiayi Li Qiandui Chen Yuheng Wu Yangfan Qi Wanqi Wang Xingzhi Chang Jie Zhang |
| author_sort | Haishao Yu |
| collection | DOAJ |
| description | Case presentationA girl aged 2 years and 5 months presented to the hospital with chief complaints of intermittent fever and weakness of the left limb for more than 1 month. The child had transient urticaria appearing on her face for 5 days. The inflammatory biomarkers were significantly increased. Brain MRI showed multiple ischemic lesions in the brain’s small vessels. The patient exhibited significant systemic inflammation and multiple vasculitis. Whole-exome sequencing showed c.1358A>G p. (Tyr453Cys) and c.1082-7T>A compound heterozygous variants in the adenosine deaminase 2 (ADA2) gene, of which the c.1082-7T>A variant has not been reported yet in previous literature. Peripheral blood mRNA reverse transcription-Sanger sequencing confirmed that this variant affected mRNA splicing, resulting in a frameshift with premature stop codon c.1083_1103del p. (Leu362Glnfs*45). Peripheral blood test suggested a significant decrease in ADA2 activity. Eventually, the patient was diagnosed with deficiency of adenosine deaminase 2 (DADA2). Her condition improved after treatment with etanercept. She had no more fevers, and no hemiplegia attacks were observed during the 3 years of follow-up.ConclusionFever and hemiplegia were the main manifestations in this patient, without typical rashes. DADA2 was finally confirmed by enzymology and genetic testing, and we believe this is the first reported case of the c.1082-7T>A intronic variant in DADA2, and the RNA studies conducted in this case have been pivotal in assessing its pathogenicity. |
| format | Article |
| id | doaj-art-f7b0ef3019414c74b836cafb56a7a61a |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj-art-f7b0ef3019414c74b836cafb56a7a61a2025-01-15T06:10:25ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-01-011510.3389/fgene.2024.14785811478581Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiencyHaishao Yu0Haishao Yu1Shuangzhu Lin2Lin Li3Jiayi Li4Qiandui Chen5Yuheng Wu6Yangfan Qi7Wanqi Wang8Xingzhi Chang9Jie Zhang10Department of Pediatrics, Yantai Yuhuangding Hospital, Shandong, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaDepartment of Pediatrics, First Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, ChinaDepartment of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Pediatrics, First Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, ChinaDepartment of Pediatrics, Changchun University of Chinese Medicine, Jilin, ChinaClinical Medical College, Norman Bethune Health Science Center of Jilin University, Changchun, ChinaDepartment of Pediatrics, Changchun University of Chinese Medicine, Jilin, ChinaDepartment of Pediatrics, Changchun University of Chinese Medicine, Jilin, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaDepartment of Pediatrics, Peking University First Hospital, Beijing, ChinaCase presentationA girl aged 2 years and 5 months presented to the hospital with chief complaints of intermittent fever and weakness of the left limb for more than 1 month. The child had transient urticaria appearing on her face for 5 days. The inflammatory biomarkers were significantly increased. Brain MRI showed multiple ischemic lesions in the brain’s small vessels. The patient exhibited significant systemic inflammation and multiple vasculitis. Whole-exome sequencing showed c.1358A>G p. (Tyr453Cys) and c.1082-7T>A compound heterozygous variants in the adenosine deaminase 2 (ADA2) gene, of which the c.1082-7T>A variant has not been reported yet in previous literature. Peripheral blood mRNA reverse transcription-Sanger sequencing confirmed that this variant affected mRNA splicing, resulting in a frameshift with premature stop codon c.1083_1103del p. (Leu362Glnfs*45). Peripheral blood test suggested a significant decrease in ADA2 activity. Eventually, the patient was diagnosed with deficiency of adenosine deaminase 2 (DADA2). Her condition improved after treatment with etanercept. She had no more fevers, and no hemiplegia attacks were observed during the 3 years of follow-up.ConclusionFever and hemiplegia were the main manifestations in this patient, without typical rashes. DADA2 was finally confirmed by enzymology and genetic testing, and we believe this is the first reported case of the c.1082-7T>A intronic variant in DADA2, and the RNA studies conducted in this case have been pivotal in assessing its pathogenicity.https://www.frontiersin.org/articles/10.3389/fgene.2024.1478581/fulldeficiency of adenosine deaminase 2ADA2 geneCECR1 genechildrenhemiplegia |
| spellingShingle | Haishao Yu Haishao Yu Shuangzhu Lin Lin Li Jiayi Li Qiandui Chen Yuheng Wu Yangfan Qi Wanqi Wang Xingzhi Chang Jie Zhang Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency Frontiers in Genetics deficiency of adenosine deaminase 2 ADA2 gene CECR1 gene children hemiplegia |
| title | Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency |
| title_full | Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency |
| title_fullStr | Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency |
| title_full_unstemmed | Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency |
| title_short | Case Report: Novel ADA2 variants cause atypical adenosine deaminase 2 deficiency |
| title_sort | case report novel ada2 variants cause atypical adenosine deaminase 2 deficiency |
| topic | deficiency of adenosine deaminase 2 ADA2 gene CECR1 gene children hemiplegia |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1478581/full |
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