Abstract
Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder, characterized by a wide clinical and genetic heterogeneity, and is the most frequent disorder of mitochondrial energy production in children. Beside its great variability in clinical, biochemical, and genetic features, LS is pathologically uniformly characterized by multifocal bilateral and symmetric spongiform degeneration of the basal ganglia, brainstem, thalamus, cerebellum, spinal cord, and optic nerves. Isolated complex I deficiency is the most common defect identified in Leigh syndrome. In 2011, the first child with a mutation of NDUFA10 gene, coding for an accessory subunits of complex I, was described. Here, we present an additional description of a child with Leigh syndrome harboring a homozygous mutation in NDUFA10, providing insights in clinical, biochemical, and neuroradiologic features for future earlier recognition.
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References
Arii J, Tanabe Y (2000) Leigh syndrome: serial MR imaging and clinical follow-up. AJNR Am J Neuroradiol 21:1502–1509
Baertling F, Rodenburg RJ, Schaper J et al (2014) A guide to diagnosis and treatment of Leigh syndrome. J Neurol Neurosurg Psychiatry 85:257–265
Baertling F, Klee D, Haack TB et al (2016) The many faces of paediatric mitochondrial disease on neuroimaging. Childs Nerv Syst 32:2077–2083
Benit P, Beugnot R, Chretien D et al (2003) Mutant NDUFV2 subunit of mitochondrial complex I causes early onset hypertrophic cardiomyopathy and encephalopathy. Hum Mutat 21:582–586
Elurbe DM, Huynen MA (2016) The origin of the supernumerary subunits and assembly factors of complex I: a treasure trove of pathway evolution. Biochim Biophys Acta 1857(7):971–979
Fassone E, Rhaman S (2012) Complex I deficiency: clinical features, biochemistry and molecular genetics. J Med Genet 49:578–590
Fassone E, Taanman JW, Hargreaves IP et al (2011) Mutations in the mithocondrial complex I assembly factor NDUFAF1 cause fatal infantile hypertrophic cardiomyopathy. J Med Genet 48:691–697
Finsterer J (2008) Leigh and Leigh-Like syndrome in children and adults. Pediatr Neurol 39:223–235
Gerards M, Sallevelt SC, Smeets HJ (2016) Leigh syndrome: resolving the clinical and genetic heterogeneity paves the way for treatment options. Mol Genet Metab 117:300–312
Giribaldi G, Doria-LAmba L, Biancheri R et al (2012) Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility. Dev Med Child Neurol 54:472–476
Haack TB, Madignier F, Herzer M et al (2012) Mutation screening of 75 candidate genes in 152 complex I deficiency cases identifies pathogenic variants in 16 genes including NDUFB9. J Med Genet 49:83–89
Haack TB, Gorza M, Danhauser K et al (2014) Phenotypic spectrum of eleven patients and five novel MTFMT mutations identified by exome sequencing and candidate gene screening. Mol Genet Metab 111:342–352
Hoefs SJ, van Spronsen FJ, Lenssen EW et al (2011) NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease. Eur J Hum Genet 19:270–274
Lake NJ, Compton AG, Rahman S, Thorburn DR (2016) Leigh syndrome: one disorder, more than 75 monogenic causes. Ann Neurol 79:190–203
Lee H-F, Tsai C-R, Chi C-S et al (2009) Leigh syndrome: clinical and neuroimaging follow-up. Pediatr Neurol 40:88–93
Leigh D (1951) Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatry 14:216–221
Lopez LC, Schuelke M, Quinzii CM et al (2006) Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations. Am J Hum Genet 79:1125–1129
Mignarri A, Rubegni A, Tessa A et al (2016) Mitochondrial dysfunction in hereditary spastic paraparesis with mutations in DDHD1/SPG28. J Neurol Sci 362:287–291
Monlleo-Neila L, Toro MD, Bornstein B et al (2013) Leigh syndrome and the mitochondrial m.13513G>A mutation: expanding the clinical spectrum. J Child Neurol 28:1531–1534
Rahman S, Blok RB, Dahl HH et al (1996) Leigh syndrome: clinical features and biochemical and DNA abnormalities. Ann Neurol 39:343–351
Rossi A, Biancheri R, Bruno C, Di Rocco M, Calvi A, Pessagno A, Tortori-Donati P (2003) Leigh syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings. AJNR Am J Neuroradiol 24:1188–1191
Ruhoy IS, Saneto RP (2014) The genetics of Leigh syndrome and its implications for clinical practice and risk management. Appl Clin Genet 7:221–234
Saneto RP, Friedman SD, Shaw DW (2008) Neuroimaging of mitochondrial diseases. Mitochondrion 8:396–413
Skladal D, Halliday J, Thorburn DR (2003) Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 126:1905–1912
Smeitink J, van der Huevel L, Di Mauro S (2001) The genetics and pathology of oxidative phosphorylation. Nat Rev Genet 2:342–352
Sofou K, De Coo IF, Isohanni P et al (2014) A multicenter study on Leigh syndrome: disease course and predictors of survival. Orphanet J Rare Dis 9:52
Tetreault M, Fahiminiya S, Antonicka H et al (2015) Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome. Hum Genet 134:981–991
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Communicated by: Daniela Karall
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Short Running Title (Synopsis)
New Clinical and Neuroradiologic Features of NDUFA10 Mutation.
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We confirm that all listed authors have provided a significant contribution in the manuscript preparation, in intellectual revision, and in patient’s care.
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Francesca Minoia, Marta Bertamino, Paolo Picco, Mariasavina Severino, Andrea Rossi, Chiara Fiorillo, Carlo Minetti, Claudia Nesti, Filippo Maria Santorelli, and Maja Di Rocco declare that they have no conflict of interest related to the present manuscript.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
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Minoia, F. et al. (2017). Widening the Heterogeneity of Leigh Syndrome: Clinical, Biochemical, and Neuroradiologic Features in a Patient Harboring a NDUFA10 Mutation. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 37. JIMD Reports, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_9
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DOI: https://doi.org/10.1007/8904_2017_9
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