{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T06:19:50Z","timestamp":1778566790520,"version":"3.51.4"},"reference-count":39,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,11,1]]},"abstract":"<jats:p>Objectives. We sought to determine the long-term clinical and biochemical outcome of newborns with mitochondrial cytopathies (MCs) and to identify possible prognostic factors that may modify the course of these diseases.<\/jats:p>\n               <jats:p>Material and Methods. Fifty-seven newborns with MCs were identified in a retrospective review (1983\u20132002). We defined 2 different outcome categories: clinical (neurologic, hepatic, myopathic, and multiorganic) and biochemical (lactate level normalization or initially normal remaining unchanged, decreased but not normalized, and persistently high). We used 2 different statistical approaches: (1) survival studies depending on the initial symptoms and lactate and enzymatic deficiencies using the Kaplan-Meier method; and (2) the same variables compared with different survival age groups and clinical and biochemical outcome categories using the \u03c72 test.<\/jats:p>\n               <jats:p>Results. Thirty-three patients died (57.8%), 12 remain alive (21%), and 12 were lost in the follow-up; 6 of them are currently older than 4 years. Most of the patients manifested multiorganic disease (64.8%) and high lactate level (77.1%) over time. Children surviving to 2.5 to 3 years of age were more likely to survive for a long period of time. Initial neurologic and hepatic presentation increased the risk to develop neurologic disease and severe persistent hyperlactacidemia, respectively. Initial severe hyperlactacidemia and combined enzyme deficiencies were significant risk factors for higher mortality and multiorganic disorders. Two patients with exclusively myopathic outcome are alive and cognitively normal at 12 years of life.<\/jats:p>\n               <jats:p>Conclusions. Children with neonatal-onset MCs have very high mortality and poor prospects. However, some with life-threatening presentations may gradually improve, giving rise to less severe diseases. Those with exclusively myopathic symptoms have a better prognosis.<\/jats:p>","DOI":"10.1542\/peds.2004-2407","type":"journal-article","created":{"date-parts":[[2005,11,1]],"date-time":"2005-11-01T18:08:50Z","timestamp":1130868530000},"page":"1170-1177","source":"Crossref","is-referenced-by-count":54,"title":["Long-term Follow-up of Neonatal Mitochondrial Cytopathies: A Study of 57 Patients"],"prefix":"10.1542","volume":"116","author":[{"given":"A.","family":"Garci\u0301a-Cazorla","sequence":"first","affiliation":[{"name":"Metabolic Diseases Unit, Department of Pediatrics, Centre Hospitalier Universitaire Necker Enfants-Malades, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"De Lonlay","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Department of Pediatrics, Centre Hospitalier Universitaire Necker Enfants-Malades, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.C.","family":"Nassogne","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Department of Pediatrics, Centre Hospitalier Universitaire Necker Enfants-Malades, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Rustin","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Research Units U375 and 30, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Touati","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Department of Pediatrics, Centre Hospitalier Universitaire Necker Enfants-Malades, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.M.","family":"Saudubray","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Department of Pediatrics, Centre Hospitalier Universitaire Necker Enfants-Malades, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2005,11,1]]},"reference":[{"key":"2021120819480317900_R1","doi-asserted-by":"crossref","unstructured":"Munnich A, Rotig A, Chretien D, et al. Clinical presentation of mitochondrial disorders in childhood. J Inherit Metab Dis.\u20081996;19:521\u2013527","DOI":"10.1007\/BF01799112"},{"key":"2021120819480317900_R2","doi-asserted-by":"crossref","unstructured":"Nissenkorn A, Zeharia A, Lev D, et al. Multiple presentation of mitochondrial disorders. Arch Dis Child.\u20081999;81:209\u2013215","DOI":"10.1136\/adc.81.3.209"},{"key":"2021120819480317900_R3","doi-asserted-by":"crossref","unstructured":"DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med.\u20082003;348:2656\u20132668","DOI":"10.1056\/NEJMra022567"},{"key":"2021120819480317900_R4","doi-asserted-by":"crossref","unstructured":"Sue CM, Hirano M, DiMauro S, De Vivo DC. Neonatal presentation of mitochondrial metabolic disorders. Semin Perinatol.\u20081999;23:113\u2013124","DOI":"10.1016\/S0146-0005(99)80045-7"},{"key":"2021120819480317900_R5","doi-asserted-by":"crossref","unstructured":"Poggi-Travert F, Martin D, Billette de Villemeur T, et al. Metabolic intermediates in lactic acidosis: compounds, samples and interpretation. J Inherit Metab Dis.\u20081996;19:478\u2013488","DOI":"10.1007\/BF01799109"},{"key":"2021120819480317900_R6","doi-asserted-by":"crossref","unstructured":"Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc.\u20081958;53:457\u2013481","DOI":"10.1080\/01621459.1958.10501452"},{"key":"2021120819480317900_R7","doi-asserted-by":"crossref","unstructured":"Ishikawa Y, Goto Y, Ishikawa Y, Minami R. Progression in a case of Kearns-Sayre syndrome. J Child Neurol.\u20082000;15:750\u2013755","DOI":"10.1177\/088307380001501107"},{"key":"2021120819480317900_R8","unstructured":"Finsterer J, Stollberger C, Blazek G, Spahits E. Cardiac involvement in myotonic dystrophy, Becker muscular dystrophy and mitochondrial myopathy: a five-year follow-up. Can J Cardiol.\u20082001;17:1061\u20131069"},{"key":"2021120819480317900_R9","doi-asserted-by":"crossref","unstructured":"Shoubridge EA. Cytochrome c oxidase deficiency. Am J Med Genet.\u20082001;106:46\u201352","DOI":"10.1002\/ajmg.1378"},{"key":"2021120819480317900_R10","doi-asserted-by":"crossref","unstructured":"Triepels RH, Van Den Heuvel LP, Trijbels JM, Smeitink JA. Respiratory chain complex I deficiency. Am J Med Genet.\u20082001;106:37\u201345","DOI":"10.1002\/ajmg.1397"},{"key":"2021120819480317900_R11","unstructured":"DiMauro S, Andreu AL, De Vivo DC. Mitochondrial disorders. J Child Neurol.\u20082002;17(suppl 3):S35\u2013S45; discussion S46\u2013S47"},{"key":"2021120819480317900_R12","doi-asserted-by":"crossref","unstructured":"Smeitink JAM. Mitochondrial disorders: clinical presentation and diagnostic dilemmas. J Inherit Metab Dis.\u20082003;26:199\u2013207","DOI":"10.1023\/A:1024489218004"},{"key":"2021120819480317900_R13","doi-asserted-by":"crossref","unstructured":"Skladal D, Sudmeler C, Konstantopoulou V, et al. Clin Pediatr (Phila).\u20082003;42:703\u2013710","DOI":"10.1177\/000992280304200806"},{"key":"2021120819480317900_R14","doi-asserted-by":"crossref","unstructured":"Zeviani M, Bertagnolio B, Uziel G. Neurologic presentations of mitochondrial diseases. J Inherit Metab Dis.\u20081996;19:504\u2013520","DOI":"10.1007\/BF01799111"},{"key":"2021120819480317900_R15","doi-asserted-by":"crossref","unstructured":"Sciacco M, Prelle A, Comi G, et al. Retrospective study of a large population of patients affected with mitochondrial disorders: clinical, morphological and molecular genetic evaluation. J Neurol.\u20082001;248:778\u2013788","DOI":"10.1007\/s004150170094"},{"key":"2021120819480317900_R16","doi-asserted-by":"crossref","unstructured":"Andreu A, DiMauro S. Current classification of mitochondrial disorders. J Neurol.\u20082003;250:1403\u20131406","DOI":"10.1007\/s00415-003-0281-3"},{"key":"2021120819480317900_R17","doi-asserted-by":"crossref","unstructured":"Ronald J, Sokol RJ, Treem WR. Mitochondria and childhood liver diseases. J Pediatr Gastroenterol Nutr.\u20081999;28:4\u201316","DOI":"10.1097\/00005176-199901000-00005"},{"key":"2021120819480317900_R18","doi-asserted-by":"crossref","unstructured":"Vilaseca MA, Briones P, Ribes A, Carreras E, Llacer A, Querol J. Fatal hepatic failure with lactic acidaemia, Fanconi syndrome and defective activity of succinate:cytochrome c reductase. J Inherit Metab Dis.\u20081991;14:285\u2013288","DOI":"10.1007\/BF01811683"},{"key":"2021120819480317900_R19","doi-asserted-by":"crossref","unstructured":"Treem WR, Sokol RJ. Disorders of mitochondria. Semin Liver Dis.\u20081998;18:237\u2013254","DOI":"10.1055\/s-2007-1007160"},{"key":"2021120819480317900_R20","doi-asserted-by":"crossref","unstructured":"Bioulac-Sage P, Parrot-Roulaud F, Mazat JP, et al. Fatal neonatal liver failure and mitochondrial cytopathy (oxidative phosphorylation deficiency): a light and electron microscopic study of the liver. Hepatology.\u20081993;18:839\u2013846","DOI":"10.1002\/hep.1840180414"},{"key":"2021120819480317900_R21","doi-asserted-by":"crossref","unstructured":"Cormier-Daire V, Chretien D, Rustin P, et al. Neonatal and delayed-onset liver involvement in disorders of oxidative phosphorylation. J Pediatr.\u20081997;130:417\u2013422","DOI":"10.1016\/S0022-3476(97)80027-3"},{"key":"2021120819480317900_R22","doi-asserted-by":"crossref","unstructured":"Mazziotta MRM, Ricci E, Bertini E, et al. Fatal infantile liver failure associated with mitochondrial DNA depletion. J Pediatr.\u20081992;121:896\u2013901","DOI":"10.1016\/S0022-3476(05)80335-X"},{"key":"2021120819480317900_R23","doi-asserted-by":"crossref","unstructured":"Bakker HD, Scholte HR, Dingemans KP, Spelbrink JN, Wijburg FA, Van den Bogert C. Depletion of mitochondrial DNA in a family with fatal neonatal liver disease. J Pediatr.\u20081996;128:683\u2013687","DOI":"10.1016\/S0022-3476(96)80135-1"},{"key":"2021120819480317900_R24","doi-asserted-by":"crossref","unstructured":"Maaswinkel-Mooij PD, Van den Bogert C, Scholte HR, Onkenhout W, Brederoo P, Poorthuis BJ. Depletion of mitochondrial DNA in the liver of a patient with lactic acidemia and hypoketotic hypoglycemia. J Pediatr.\u20081996;128:679\u2013682","DOI":"10.1016\/S0022-3476(96)80134-X"},{"key":"2021120819480317900_R25","doi-asserted-by":"crossref","unstructured":"Leshinsky-Silver E, Levine A, Nissenkorn A, et al. Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency. Mol Genet Metab.\u20082003;79:288\u2013293","DOI":"10.1016\/S1096-7192(03)00097-0"},{"key":"2021120819480317900_R26","doi-asserted-by":"crossref","unstructured":"Rabinowitzs SS, Gelfond D, Chen CK, et al. Hepatocerebral mitochondrial DNA depletion syndrome: clinical and morphologic features of a nuclear gene mutation. J Pediatr Gastroenterol Nutr.\u20082004;38:216\u2013220","DOI":"10.1097\/00005176-200402000-00022"},{"key":"2021120819480317900_R27","doi-asserted-by":"crossref","unstructured":"Carrozzo R, Bornstein B, Lucioli S, et al. Mutation analysis in 16 patients with mtDNA depletion. Hum Mutat.\u20082003;21:453\u2013454","DOI":"10.1002\/humu.9135"},{"key":"2021120819480317900_R28","doi-asserted-by":"crossref","unstructured":"Elpeleg O, Mandel H, Saada A. Depletion of the other genome-mitochondrial DNA depletion syndromes in humans. J Mol Med.\u20082002;80:389\u2013396","DOI":"10.1007\/s00109-002-0343-5"},{"key":"2021120819480317900_R29","doi-asserted-by":"crossref","unstructured":"Korenge G, Bentlage H, Ruitenbeek W, et al. Isolated and combined deficiencies of NADH dehydrogenase (complex I) in muscle tissues of children with mitochondrial myopathies. Eur J Pediatr.\u20081990;150:104\u2013108","DOI":"10.1007\/BF02072049"},{"key":"2021120819480317900_R30","doi-asserted-by":"crossref","unstructured":"Loeffen JL, Smeitink JA, Trijbels JM, et al. Isolated complex I deficiency in children: clinical, biochemical and genetic aspects. Hum Mutat.\u20082000;15:123\u2013134","DOI":"10.1002\/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P"},{"key":"2021120819480317900_R31","doi-asserted-by":"crossref","unstructured":"Kirby DM, Crawford M, Cleary MA, Dahl HH, Dennett X, Thorburn DR. Respiratory chain complex I deficiency: an underdiagnosed energy generation disorder. Neurology.\u20081999;52:1255\u20131264","DOI":"10.1212\/WNL.52.6.1255"},{"key":"2021120819480317900_R32","doi-asserted-by":"crossref","unstructured":"DiMauro S, Nicholson J, Hays A, et al. Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency. Ann Neurol.\u20081983;14:226\u2013234","DOI":"10.1002\/ana.410140209"},{"key":"2021120819480317900_R33","doi-asserted-by":"crossref","unstructured":"Zeviani M, Koga Y, Shikura K, et al. Benign reversible muscle cytochrome c oxidase deficiency: a second case. Neurology.\u20081987;37:64\u201367","DOI":"10.1212\/WNL.37.1.64"},{"key":"2021120819480317900_R34","unstructured":"Servedei S, Bertini E, Dionisi-Vici C. Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency: a third case. Clin Neuropathol.\u20081988;7:209\u2013210"},{"key":"2021120819480317900_R35","unstructured":"Castro-Gago M, Eiri\u0301s J, Pintos E, et al. Benign congenital myopathy associated with a partial deficiency of complexes I and III of the mitochondrial respiratory chain [in Spanish]. Rev Neurol.\u20082000;31:838\u2013841"},{"key":"2021120819480317900_R36","doi-asserted-by":"crossref","unstructured":"Pons R, Andreetta F, Wang CH, et al. Mitochondrial myopathy simulating spinal muscular atrophy. Pediatr Neurol.\u20081996;15:153\u2013158","DOI":"10.1016\/0887-8994(96)00118-X"},{"key":"2021120819480317900_R37","doi-asserted-by":"crossref","unstructured":"Salo MK, Rapola J, Somer H, et al. Reversible mitochondrial myopathy with cytochrome c oxidase deficiency. Arch Dis Child.\u20081992;67:1033\u20131035","DOI":"10.1136\/adc.67.8.1033"},{"key":"2021120819480317900_R38","doi-asserted-by":"crossref","unstructured":"Ducluzeau PH, Lachaux A, Bouvier R, et al. Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion. J Hepatol.\u20082002;36:698\u2013703","DOI":"10.1016\/S0168-8278(02)00021-1"},{"key":"2021120819480317900_R39","doi-asserted-by":"crossref","unstructured":"Lev D, Gilad E, Leshinsky-Silver E, et al. Reversible fulminant lactic acidosis and liver failure in an infant with hepatic cytochrome-c oxidase deficiency. J Inherit Metab Dis.\u20082002;25:371\u2013377","DOI":"10.1023\/A:1020195616081"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/116\/5\/1170\/1025317\/zpe01105001170.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/116\/5\/1170\/1025317\/zpe01105001170.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,8]],"date-time":"2021-12-08T22:46:19Z","timestamp":1639003579000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/116\/5\/1170\/68044\/Long-term-Follow-up-of-Neonatal-Mitochondrial"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11,1]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2005,11,1]]},"published-print":{"date-parts":[[2005,11,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2004-2407","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11,1]]}}}