{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T19:02:58Z","timestamp":1774551778822,"version":"3.50.1"},"reference-count":26,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"\n Summary<\/jats:title>\n \n Mitochondrial diseases cause systemic failure of energy production and can manifest as various disorders of hormone production and secretion from endocrine organs. These effects can prevent normal growth in children, resulting in adults of short stature. We therefore explored the nutritional and endocrinological status of pediatric mitochondrial disease patients with impaired growth. Four Japanese patients with genetically diagnosed mitochondrial disease were studied (one male and three females, aged 4\u201322 years). The age of onset ranged from 0 months to 7 years, and the causal genes identified were\n mtDNA<\/jats:italic>\n ,\n PDHA1<\/jats:italic>\n , and\n NARS2<\/jats:italic>\n (in two sibling patients). Two patients were diagnosed with small for gestational age at birth, and their current height standard deviation scores ranged from \u22121.9 SD to \u22126.4 SD. Mitochondrial diseases can present as impaired growth with dysfunction of various organs, depending on the causal gene and the degree of heteroplasmy. Our patients had demonstrated low T3 syndrome and reduced IGF1 levels, which appeared to be influenced by impaired nutritional status. These findings emphasize the need for careful monitoring of growth trajectories alongside nutritional and endocrine evaluations to improve clinical management.\n <\/jats:p>\n <\/jats:sec>\n \n Learning points<\/jats:title>\n \n \n Mitochondrial diseases can disrupt endocrine function involving the GH\u2013IGF1 axis and the thyroid and gonadal systems, leading to impaired growth during childhood.<\/jats:p>\n <\/jats:list-item>\n \n Patients with early-onset mitochondrial disease tend to experience severe symptoms and pronounced growth impairment.<\/jats:p>\n <\/jats:list-item>\n \n Children with mitochondrial diseases often show low IGF1 levels, low T3 syndrome, and delayed bone age, reflecting endocrine dysfunction commonly observed in chronic systemic diseases and the further influence of suboptimal nutritional status.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:sec>","DOI":"10.1530\/edm-25-0140","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T11:16:09Z","timestamp":1771413369000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":0,"title":["Nutrient and endocrine factors affecting impaired growth in pediatric mitochondrial diseases"],"prefix":"10.1530","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-1715","authenticated-orcid":true,"given":"Hideaki","family":"Yagasaki","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromune","family":"Narusawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumikazu","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Fujioka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonoko","family":"Mizorogi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshimi","family":"Kaga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Inukai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Lancet","first-page":"1825","article-title":"Mitochondrial diseases","volume":"379","author":"Schapira AH","year":"2012","unstructured":"Schapira AH\n\n. Mitochondrial diseases. Lancet 2012 379 1825\u20131834. (https:\/\/doi.org\/10.1016\/s0140-6736(11)61305-6)"},{"key":"bib2","series-title":"Annu Rev Genom Hum Genet","first-page":"257","article-title":"Recent advances in mitochondrial disease","volume":"18","author":"Craven L","year":"2017","unstructured":"Craven L\n, \nAlston CL\n, \nTaylor RW\n, et al.\n Recent advances in mitochondrial disease. Annu Rev Genom Hum Genet 2017 18 257\u2013275. (https:\/\/doi.org\/10.1146\/annurev-genom-091416-035426)"},{"key":"bib3","series-title":"Front Physiol","article-title":"Mitochondria: it is all about energy","volume":"14","author":"Casanova A","year":"2023","unstructured":"Casanova A\n, \nWevers A\n, \nNavarro-Ledesma S\n, et al.\n Mitochondria: it is all about energy. Front Physiol 2023 14 1114231. (https:\/\/doi.org\/10.3389\/fphys.2023.1114231)"},{"key":"bib4","series-title":"Arch Dis Child","first-page":"1082","article-title":"Recognition, investigation and management of mitochondrial disease.","volume":"102","author":"Davison JE","year":"2017","unstructured":"Davison JE\n & \nRahman S\n\n. Recognition, investigation and management of mitochondrial disease. Arch Dis Child 2017 102 1082\u20131090 28647693. (https:\/\/doi.org\/10.1136\/archdischild-2016-311370)"},{"key":"bib5","series-title":"J Intern Med","first-page":"609","article-title":"Mitochondrial disease in children","volume":"287","author":"Rahman S","year":"2020","unstructured":"Rahman S\n\n. Mitochondrial disease in children. J Intern Med 2020 287 609\u2013633. (https:\/\/doi.org\/10.1111\/joim.13054)"},{"key":"bib6","series-title":"J Clin Endocrinol Metab","first-page":"2057","article-title":"Height as a clinical biomarker of disease burden in adult mitochondrial disease","volume":"104","author":"Boal RL","year":"2019","unstructured":"Boal RL\n, \nNg YS\n, \nPickett SJ\n, et al.\n Height as a clinical biomarker of disease burden in adult mitochondrial disease. J Clin Endocrinol Metab 2019 104 2057\u20132066. (https:\/\/doi.org\/10.1210\/jc.2018-00957)"},{"key":"bib7","series-title":"EBioMedicine","article-title":"Pharmacological advances in mitochondrial therapy","volume":"65","author":"Singh A","year":"2021","unstructured":"Singh A\n, \nFaccenda D\n & \nCampanella M\n\n. Pharmacological advances in mitochondrial therapy. EBioMedicine 2021 65 103244. (https:\/\/doi.org\/10.1016\/j.ebiom.2021.103244)"},{"key":"bib8","series-title":"Pediatr Neonatol","first-page":"475","article-title":"Hypothermic reaction after infection in an infant with pyruvate dehydrogenase complex deficiency","volume":"60","author":"Yagasaki H","year":"2019","unstructured":"Yagasaki H\n, \nOhyama T\n, \nNarusawa H\n, et al.\n Hypothermic reaction after infection in an infant with pyruvate dehydrogenase complex deficiency. Pediatr Neonatol 2019 60 475\u2013476. (https:\/\/doi.org\/10.1016\/j.pedneo.2019.04.005)"},{"key":"bib9","series-title":"Am J Med Genet","first-page":"2466","article-title":"Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome","volume":"188","author":"Yagasaki H","year":"2022","unstructured":"Yagasaki H\n, \nSano F\n, \nNarusawa H\n, et al.\n Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome. Am J Med Genet 2022 188 2466\u20132471. (https:\/\/doi.org\/10.1002\/ajmg.a.62873)"},{"key":"bib10","series-title":"J Pediatr Endocrinol Metab","first-page":"1003","article-title":"Growth hormone deficiency in a patient with mitochondrial disease","volume":"28","author":"Rocha V","year":"2015","unstructured":"Rocha V\n, \nRocha D\n, \nSantos H\n, et al.\n Growth hormone deficiency in a patient with mitochondrial disease. J Pediatr Endocrinol Metab 2015 28 1003\u20131004. (https:\/\/doi.org\/10.1515\/jpem-2014-0315)"},{"key":"bib11","series-title":"J Cell Mol Med","first-page":"10100","article-title":"Postnatal growth retardation is associated with intestinal mucosa mitochondrial dysfunction and aberrant energy status in piglets","volume":"24","author":"Qi M","year":"2020","unstructured":"Qi M\n, \nWang J\n, \nTan B\n, et al.\n Postnatal growth retardation is associated with intestinal mucosa mitochondrial dysfunction and aberrant energy status in piglets. J Cell Mol Med 2020 24 10100\u201310111. (https:\/\/doi.org\/10.1111\/jcmm.15621)"},{"key":"bib12","series-title":"J Endocr Soc","first-page":"361","article-title":"Endocrine disorders in primary mitochondrial disease","volume":"2","author":"Al-Gadi IS","year":"2018","unstructured":"Al-Gadi IS\n, \nHaas RH\n, \nFalk MJ\n, et al.\n Endocrine disorders in primary mitochondrial disease. J Endocr Soc 2018 2 361\u2013373. (https:\/\/doi.org\/10.1210\/js.2017-00434)"},{"key":"bib13","series-title":"Eur J Pediatr","first-page":"425","article-title":"Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease","volume":"180","author":"Chae HW","year":"2021","unstructured":"Chae HW\n, \nNa JH\n, \nKwon A\n, et al.\n Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease. Eur J Pediatr 2021 180 425\u2013432. (https:\/\/doi.org\/10.1007\/s00431-020-03804-3)"},{"key":"bib1","series-title":"Lancet","first-page":"1825","article-title":"Mitochondrial diseases","volume":"379","author":"Schapira AH","year":"2012","unstructured":"Schapira AH\n\n. Mitochondrial diseases. Lancet 2012 379 1825\u20131834. (https:\/\/doi.org\/10.1016\/s0140-6736(11)61305-6)"},{"key":"bib2","series-title":"Annu Rev Genom Hum Genet","first-page":"257","article-title":"Recent advances in mitochondrial disease","volume":"18","author":"Craven L","year":"2017","unstructured":"Craven L\n, \nAlston CL\n, \nTaylor RW\n, et al.\n Recent advances in mitochondrial disease. Annu Rev Genom Hum Genet 2017 18 257\u2013275. (https:\/\/doi.org\/10.1146\/annurev-genom-091416-035426)"},{"key":"bib3","series-title":"Front Physiol","article-title":"Mitochondria: it is all about energy","volume":"14","author":"Casanova A","year":"2023","unstructured":"Casanova A\n, \nWevers A\n, \nNavarro-Ledesma S\n, et al.\n Mitochondria: it is all about energy. Front Physiol 2023 14 1114231. (https:\/\/doi.org\/10.3389\/fphys.2023.1114231)"},{"key":"bib4","series-title":"Arch Dis Child","first-page":"1082","article-title":"Recognition, investigation and management of mitochondrial disease.","volume":"102","author":"Davison JE","year":"2017","unstructured":"Davison JE\n & \nRahman S\n\n. Recognition, investigation and management of mitochondrial disease. Arch Dis Child 2017 102 1082\u20131090 28647693. (https:\/\/doi.org\/10.1136\/archdischild-2016-311370)"},{"key":"bib5","series-title":"J Intern Med","first-page":"609","article-title":"Mitochondrial disease in children","volume":"287","author":"Rahman S","year":"2020","unstructured":"Rahman S\n\n. Mitochondrial disease in children. J Intern Med 2020 287 609\u2013633. (https:\/\/doi.org\/10.1111\/joim.13054)"},{"key":"bib6","series-title":"J Clin Endocrinol Metab","first-page":"2057","article-title":"Height as a clinical biomarker of disease burden in adult mitochondrial disease","volume":"104","author":"Boal RL","year":"2019","unstructured":"Boal RL\n, \nNg YS\n, \nPickett SJ\n, et al.\n Height as a clinical biomarker of disease burden in adult mitochondrial disease. J Clin Endocrinol Metab 2019 104 2057\u20132066. (https:\/\/doi.org\/10.1210\/jc.2018-00957)"},{"key":"bib7","series-title":"EBioMedicine","article-title":"Pharmacological advances in mitochondrial therapy","volume":"65","author":"Singh A","year":"2021","unstructured":"Singh A\n, \nFaccenda D\n & \nCampanella M\n\n. Pharmacological advances in mitochondrial therapy. EBioMedicine 2021 65 103244. (https:\/\/doi.org\/10.1016\/j.ebiom.2021.103244)"},{"key":"bib8","series-title":"Pediatr Neonatol","first-page":"475","article-title":"Hypothermic reaction after infection in an infant with pyruvate dehydrogenase complex deficiency","volume":"60","author":"Yagasaki H","year":"2019","unstructured":"Yagasaki H\n, \nOhyama T\n, \nNarusawa H\n, et al.\n Hypothermic reaction after infection in an infant with pyruvate dehydrogenase complex deficiency. Pediatr Neonatol 2019 60 475\u2013476. (https:\/\/doi.org\/10.1016\/j.pedneo.2019.04.005)"},{"key":"bib9","series-title":"Am J Med Genet","first-page":"2466","article-title":"Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome","volume":"188","author":"Yagasaki H","year":"2022","unstructured":"Yagasaki H\n, \nSano F\n, \nNarusawa H\n, et al.\n Compound heterozygous variants of the NARS2 gene in siblings with developmental delay, epilepsy, and neonatal diabetes syndrome. Am J Med Genet 2022 188 2466\u20132471. (https:\/\/doi.org\/10.1002\/ajmg.a.62873)"},{"key":"bib10","series-title":"J Pediatr Endocrinol Metab","first-page":"1003","article-title":"Growth hormone deficiency in a patient with mitochondrial disease","volume":"28","author":"Rocha V","year":"2015","unstructured":"Rocha V\n, \nRocha D\n, \nSantos H\n, et al.\n Growth hormone deficiency in a patient with mitochondrial disease. J Pediatr Endocrinol Metab 2015 28 1003\u20131004. (https:\/\/doi.org\/10.1515\/jpem-2014-0315)"},{"key":"bib11","series-title":"J Cell Mol Med","first-page":"10100","article-title":"Postnatal growth retardation is associated with intestinal mucosa mitochondrial dysfunction and aberrant energy status in piglets","volume":"24","author":"Qi M","year":"2020","unstructured":"Qi M\n, \nWang J\n, \nTan B\n, et al.\n Postnatal growth retardation is associated with intestinal mucosa mitochondrial dysfunction and aberrant energy status in piglets. J Cell Mol Med 2020 24 10100\u201310111. (https:\/\/doi.org\/10.1111\/jcmm.15621)"},{"key":"bib12","series-title":"J Endocr Soc","first-page":"361","article-title":"Endocrine disorders in primary mitochondrial disease","volume":"2","author":"Al-Gadi IS","year":"2018","unstructured":"Al-Gadi IS\n, \nHaas RH\n, \nFalk MJ\n, et al.\n Endocrine disorders in primary mitochondrial disease. J Endocr Soc 2018 2 361\u2013373. (https:\/\/doi.org\/10.1210\/js.2017-00434)"},{"key":"bib13","series-title":"Eur J Pediatr","first-page":"425","article-title":"Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease","volume":"180","author":"Chae HW","year":"2021","unstructured":"Chae HW\n, \nNa JH\n, \nKwon A\n, et al.\n Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease. Eur J Pediatr 2021 180 425\u2013432. (https:\/\/doi.org\/10.1007\/s00431-020-03804-3)"}],"container-title":["Endocrinology, Diabetes & Metabolism Case Reports"],"original-title":[],"link":[{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2026\/1\/EDM-25-0140.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2026\/1\/EDM-25-0140.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/edm.bioscientifica.com\/downloadpdf\/journals\/edm\/2026\/1\/EDM-25-0140.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:20:14Z","timestamp":1774549214000},"score":1,"resource":{"primary":{"URL":"https:\/\/edm.bioscientifica.com\/view\/journals\/edm\/2026\/1\/EDM-25-0140.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":26,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/edm-25-0140","relation":{},"ISSN":["2052-0573"],"issn-type":[{"value":"2052-0573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]}}}