{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T20:24:34Z","timestamp":1785183874560,"version":"3.55.0"},"reference-count":14,"publisher":"Walter de Gruyter GmbH","issue":"2","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Pathogenic variants in\n                      <jats:italic>TARS2<\/jats:italic>\n                      are associated with combined oxidative phosphorylation deficiency 21 (COXPD21), an autosomal recessive disorder usually presenting as mitochondrial encephalomyopathy. Kidney impairment has been documented in a minority of COXPD21 patients, mostly with distal renal tubular acidosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case report<\/jats:title>\n                    <jats:p>\n                      We report on the first COXPD21 patient with generalized tubular dysfunction and early childhood progression to chronic kidney disease (CKD). Thorough diagnostic evaluation was initiated at six months of age due to failure to thrive, muscular hypotonia, motor delay and recurrent bronchiolitis. The boy was lost to follow-up until the age of two years, when he was readmitted with elevated creatinine level, reduced estimated glomerular filtrate rate, normochromic anaemia, metabolic acidosis and hyperkalaemia. Urine abnormalities pointed to generalized tubular dysfunction. Two novel heterozygous missense variants in\n                      <jats:italic>TARS2<\/jats:italic>\n                      gene were detected by the means of whole exome sequencing: c.1298T&gt;G (p.Phe438Cys) of maternal origin and c.1931A&gt;T (p.Asp644Val) of paternal origin. Currently, at 4.5 years of age, the boy has failure to thrive, severe motor and verbal delay and end stage of CKD. We referred the patient to paediatric centre that provides renal replacement therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The overall clinical course in the patient we report on corresponds well to the previously reported cases of\n                      <jats:italic>TARS2<\/jats:italic>\n                      related COXPD21, especially in regard to neurological and developmental aspects of the disease. However, we point out the generalized tubulopathy and early occurrence of CKD in our patient as atypical renal involvement in COXPD21. Additionally, this is the first report of hypothyroidism and hypoparathyroidism in a COXPD21 patient.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2478\/bjmg-2023-0016","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T17:42:04Z","timestamp":1710265324000},"page":"59-64","source":"Crossref","is-referenced-by-count":1,"title":["Expanding the Phenotypic Spectrum: Chronic Kidney Disease in a Patient with Combined Oxidative Phosphorylation Defect 21"],"prefix":"10.2478","volume":"26","author":[{"given":"A","family":"Paripovi\u0107","sequence":"first","affiliation":[{"name":"Department of Nephrology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d , Belgrade , Serbia"},{"name":"University of Belgrade, Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Maver","sequence":"additional","affiliation":[{"name":"Clinical Institute of Genomic Medicine , University Medical Centre Ljubljana , Ljubljana , Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Staji\u0107","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d , Belgrade , Serbia"},{"name":"University of Belgrade, Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Putnik","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d , Belgrade , Serbia"},{"name":"University of Belgrade, Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Ostoji\u0107","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d , Belgrade , Serbia"},{"name":"University of Belgrade, Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Alimpi\u0107","sequence":"additional","affiliation":[{"name":"Day Care Hospital, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Ili\u0107","sequence":"additional","affiliation":[{"name":"Clinical Genetics Outpatient Clinic, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d , Belgrade , Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Sarajlija","sequence":"additional","affiliation":[{"name":"Clinical Genetics Outpatient Clinic, Mother and Child Health Care Institute of Serbia \u201cDr Vukan \u010cupi\u0107\u201d , Belgrade , Serbia"},{"name":"University of Belgrade, Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"2026042716344670251_j_bjmg-2023-0016_ref_001","doi-asserted-by":"crossref","unstructured":"Diodato D, Melchionda L, Haack TB, Dallabona C, Baruffini E, Donnini C, et al. VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies. Hum Mutat. 2014; 35(8):983\u20139.","DOI":"10.1002\/humu.22590"},{"key":"2026042716344670251_j_bjmg-2023-0016_ref_002","doi-asserted-by":"crossref","unstructured":"Accogli A, Lin SJ, Severino M, Kim SH, Huang K, Rocca C, et al. Clinical, neuroradiological, and molecular characterization of mitochondrial threonyltRNA-synthetase (TARS2)-related disorder. Genet Med. 2023; 25(11):100938.","DOI":"10.1016\/j.gim.2023.100938"},{"key":"2026042716344670251_j_bjmg-2023-0016_ref_003","doi-asserted-by":"crossref","unstructured":"He P, Wang Q, Hong X, Yuan H. Novel TARS2 variant identified in a Chinese patient with mitochondrial encephalomyopathy and a systematic review. Am J Med Genet A. 2023; 191(1):70\u20136.","DOI":"10.1002\/ajmg.a.62988"},{"key":"2026042716344670251_j_bjmg-2023-0016_ref_004","doi-asserted-by":"crossref","unstructured":"Zheng WQ, Pedersen SV, Thompson K, Bellacchio E, French CE, Munro B, et al. Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease. Hum Mol Genet. 2022; 31(4):523\u201334.","DOI":"10.1093\/hmg\/ddab257"},{"key":"2026042716344670251_j_bjmg-2023-0016_ref_005","doi-asserted-by":"crossref","unstructured":"Li X, Peng B, Hou C, Li J, Zeng Y, Wu W, Liao Y, et al. Novel compound heterozygous TARS2 variants in a Chinese family with mitochondrial encephalomyopathy: a case report. BMC Med Genet. 2020; 21(1):217.","DOI":"10.1186\/s12881-020-01149-0"},{"key":"2026042716344670251_j_bjmg-2023-0016_ref_006","doi-asserted-by":"crossref","unstructured":"Parasyri M, Brandstr\u00f6m P, Uusimaa J, Ostergaard E, Hikmat O, Isohanni P, et al. Renal Phenotype in Mitochondrial Diseases: A Multicenter Study. Kidney Dis (Basel). 2022; 8(2):148\u201359.","DOI":"10.1159\/000521148"},{"key":"2026042716344670251_j_bjmg-2023-0016_ref_007","doi-asserted-by":"crossref","unstructured":"Finsterer J, Scorza FA. 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