{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T05:53:30Z","timestamp":1769234010819,"version":"3.49.0"},"reference-count":21,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T00:00:00Z","timestamp":1633305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770710"],"award-info":[{"award-number":["81770710"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Plan of Zhejiang Province","award":["2019C03028"],"award-info":[{"award-number":["2019C03028"]}]},{"name":"Zhejiang province, and National Health Commission","award":["WKJ-ZJ-1908"],"award-info":[{"award-number":["WKJ-ZJ-1908"]}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ18H050001"],"award-info":[{"award-number":["LQ18H050001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Fanconi syndrome is one of the primary renal manifestations of mitochondrial cytopathies caused by mitochondrial DNA (mtDNA) mutation. The common 4977-bp mtDNA deletion has been reported to be associated with aging and diseases involving multiple extrarenal organs. Cases of Fanconi syndrome caused by the 4977-bp deletion were rarely reported previously. Here, we report a 6-year-old girl with growth retardation in the course of Fanconi syndrome. She had mild ptosis and pigmented retinopathy. Abnormal biochemical findings included low-molecular-weight proteinuria, normoglycemic glycosuria, increased urine phosphorus excretion, metabolic acidosis, and hypophosphatemia. Growth records showed that her body weight and height were normal in the first year and failed to thrive after the age of three. Using a highly sensitive mtDNA analysis methodology, she was identified to possess the common 4977-bp mtDNA deletion. The mutation rate was 84.7% in the urine exfoliated cells, 78.67% in the oral mucosal cells, and 23.99% in the blood sample. After three months of oral coenzyme Q10 and levocarnitine treatment in combination with standard electrolyte supplement, her condition was improved. This is a report of growth retardation as the initial major clinical presentation of Fanconi syndrome caused by the deletion of the 4977-bp fragment. Renal tubular abnormality without any other extrarenal dysfunction may be an initial clinical sign of mitochondrial disorders. Moreover, considering the heterogeneity of the phenotypes associated with mtDNA mutations, the risk of developing Kearns\u2013Sayre syndrome (KSS) with age in this patient should be noted because she had ptosis, retinal involvement, and changes in the brain and skeletal muscle.<\/jats:p>","DOI":"10.3390\/children8100887","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T09:24:15Z","timestamp":1633339455000},"page":"887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Growth Retardation in the Course of Fanconi Syndrome Caused by the 4977-bp Mitochondrial DNA Deletion: A Case Report"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7125-0224","authenticated-orcid":false,"given":"Ting","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nephrology, The Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, 3333 Binsheng Road, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, 3333 Binsheng Road, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, 3333 Binsheng Road, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, 3333 Binsheng Road, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haidong","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, 3333 Binsheng Road, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-3806","authenticated-orcid":false,"given":"Jianhua","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Children\u2019s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children\u2019s Regional Medical Center, 3333 Binsheng Road, Hangzhou 310052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.pcl.2018.09.002","article-title":"Fanconi Syndrome","volume":"66","author":"Foreman","year":"2019","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00467-019-04404-6","article-title":"Mitochondrial DNA Mutations in Renal Disease: An Overview","volume":"36","author":"Govers","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1046\/j.1432-1327.1998.2570192.x","article-title":"Bioenergetic Consequences of Accumulating the Common 4977-Bp Mitochondrial DNA Deletion","volume":"257","author":"Porteous","year":"1998","journal-title":"Eur. J. Biochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1007\/BF00865468","article-title":"Deletion of the Mitochondrial DNA in a Case of de Toni-Debr\u00e9-Fanconi Syndrome and Pearson Syndrome","volume":"8","author":"Niaudet","year":"1994","journal-title":"Pediatr. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s00467-011-2096-2","article-title":"A Mitochondrial DNA Deletion Presenting with Corneal Clouding and Severe Fanconi Syndrome","volume":"27","author":"Lee","year":"2012","journal-title":"Pediatr. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s00467-006-0288-y","article-title":"Mitochondrial DNA Deletion in a Girl with Fanconi\u2019s Syndrome","volume":"22","author":"Au","year":"2007","journal-title":"Pediatr. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s00467-004-1473-5","article-title":"De Toni-Debr\u00e9-Fanconi Syndrome Due to a Palindrome-Flanked Deletion in Mitochondrial DNA","volume":"19","author":"Solano","year":"2004","journal-title":"Pediatr. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1038\/ki.1994.181","article-title":"Mitochondrial DNA Deletion: A Cause of Chronic Tubulointerstitial Nephropathy","volume":"45","author":"Szabolcs","year":"1994","journal-title":"Kidney Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1055\/s-2007-962854","article-title":"Patient with Fanconi Syndrome (FS) and Retinitis Pigmentosa (RP) Caused by a Deletion and Duplication of Mitochondrial DNA (MtDNA)","volume":"224","author":"Pitchon","year":"2007","journal-title":"Klin. Monbl. Augenheilkd."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/BF00711812","article-title":"Complex I Deficiency with Diabetes, Fanconi Syndrome and MtDNA Deletion","volume":"17","author":"Luder","year":"1994","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00431-012-1798-1","article-title":"A Rare Case Report of Simultaneous Presentation of Myopathy, Addison\u2019s Disease, Primary Hypoparathyroidism, and Fanconi Syndrome in a Child Diagnosed with Kearns-Sayre Syndrome","volume":"172","author":"Tzoufi","year":"2013","journal-title":"Eur. J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/ajmg.1320380417","article-title":"Renal and Skin Involvement in a Patient with Complete Kearns-Sayre Syndrome","volume":"38","author":"Mori","year":"1991","journal-title":"Am. J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1752-1947-3-101","article-title":"De Toni-Debr\u00e9-Fanconi Syndrome in a Patient with Kearns-Sayre Syndrome: A Case Report","volume":"3","author":"Mihai","year":"2009","journal-title":"J. Med. Case Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ejmg.2008.10.003","article-title":"Tubulopathy and Pancytopaenia with Normal Pancreatic Function: A Variant of Pearson Syndrome","volume":"52","author":"Atale","year":"2009","journal-title":"Eur. J. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/BF02072515","article-title":"Pearson Bone Marrow-Pancreas Syndrome with Insulin-Dependent Diabetes, Progressive Renal Tubulopathy, Organic Aciduria and Elevated Fetal Haemoglobin Caused by Deletion and Duplication of Mitochondrial DNA","volume":"152","author":"Schoenle","year":"1993","journal-title":"Eur. J. Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1203\/00006450-199110000-00007","article-title":"Congenital Hypoplastic Anemia, Diabetes, and Severe Renal Tubular Dysfunction Associated with a Mitochondrial Dna Deletion","volume":"30","author":"Majander","year":"1991","journal-title":"Pediatr. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0887-8994(95)00082-Q","article-title":"Mitochondrial DNA Deletion in a Patient with Mitochondrial Myopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) and Fanconi\u2019s Syndrome","volume":"13","author":"Campos","year":"1995","journal-title":"Pediatr. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.pedneo.2011.08.013","article-title":"A Novel 3670-Base Pair Mitochondrial DNA Deletion Resulting in Multi-Systemic Manifestations in a Child","volume":"53","author":"Liu","year":"2012","journal-title":"Pediatr. Neonatol."},{"key":"ref_19","unstructured":"Goldstein, A., and Falk, M.J. (1993). Mitochondrial DNA Deletion Syndromes. GeneReviews\u00ae, University of Washington."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e16302","DOI":"10.1097\/MD.0000000000016302","article-title":"Correlation between Mitochondrial DNA 4977bp Deletion and Presbycusis: A System Review and Meta-Analysis","volume":"98","author":"Han","year":"2019","journal-title":"Medicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.3109\/19401736.2015.1063046","article-title":"Age-Related Decrease in MtDNA Content as a Consequence of MtDNA 4977 Bp Deletion","volume":"27","author":"Diba","year":"2016","journal-title":"Mitochondrial DNA"}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/10\/887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:09:24Z","timestamp":1760166564000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/8\/10\/887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,4]]},"references-count":21,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["children8100887"],"URL":"https:\/\/doi.org\/10.3390\/children8100887","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,4]]}}}