Abstract
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by a combination of reciprocal social deficits, communication impairment, and rigid ritualistic interest and stereotypies. The etiology is generally multifactorial, including genetic, immunological and/or environmental factors. A group of ASD has been linked to mitochondrial dysfunction with subsequent deficiency in energy production. Patients with ASD and mitochondrial disease often show signs and symptoms uncommon to idiopathic ASD such as cardiac, pancreatic or liver dysfunction, cardiac, growth retardation, fatigability, but in some cases semiology is different. We show two clinical cases of ASD associated to a deficiency of the mitochondrial respiratory chain (complex I+III and IV) with different clinical presentations. In one case, signs and symptoms of mitochondrial disorder were mild and the second diagnosis was attained many years after that of ASD. These findings support the recent growing body of evidence that ASD can be associated with mitochondrial disorder. Children with ASD and abnormal neurologic or systemic findings should be evaluated for mitochondrial disorder.
Similar content being viewed by others
References
Al-Mosalem OA, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to energy metabolism in Saudi autistic children. Clin Biochem 42(10–11):949–957
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders (Revised 4th ed.). Washington
Anitha A, Nakamura K, Thanseem I, Matsuzaki H, Miyachi T, Tsujii M, Iwata Y, Suzuki K, Sugiyama T, Mori N (2012) Downregulation of the expression of mitochondrial electron transport complex genes in autism brains. Brain Pathol. doi:10.1111/bpa.12002
Barragan-Campos HM, Valee J-N, Lo D, Barrera-Ramirez F, Argote-Greene M, Sanchez-Guerrero J, Estanol B, Guillevin R, Chiras J (2005) Brain magnetic resonance imaging findings in patients with mitochondrial cytopathies. Arch Neurol 62:737–742
Chauhan A, Gu F, Essa MM, Wegiel J, Kaur K, Brown WT, Chauhan V (2011) Brain region-specific deficit in mitochondrial electron transport chain complexes in children with autism. J Neurochem 117(2):209–220
Chinnery P, Majamaa K, Turnbull D, Thorburn D (2006) Treatment for mitochondrial disorders. Cochrane Database Syst Rev (1):CD004426
Coleman M, Blass JP (1985) Autism and lactic acidosis. J Autism Dev Disord 15(1):1–8
Dhillon S, Hellings JA, Butler MG (2011) Genetics and mitochondrial abnormalities in autism spectrum disorders: a review. Curr Genomics 12(5):322–332
Di Mauro S, Mancuso M (2007) Mitochondrial diseases: therapeutic approaches. Biosci Rep 27(1–3):125–137
Di Mauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348(26):2656–2668
Dinopoulos A, Cecil KM, Schapiro MB, Papadimitriou A, Hadjigeorglou GM, Wong B, de Grauw T, Egelhoff JC (2005) Brain MRI and proton MRS findings in infants and children with respiratory chain defects. Neuropediatrics 36:290–301
Filipek PA, Juranek J, Cummings KA, Gallardo P, Yuan, Gargus JJ (2004) Relative carnitine deficiency in autism. J Autism Dev Disord 34:615–623
Fillano JJ, Goldenthal MJ, Rhodes CH, Marín-García J (2002) Mitochondrial dysfunction in patients with hypotonia, epilepsy, autism, and developmental delay: HEADD syndrome. J Child Neurol 17(6):435–439
Folstein SE, Rosen-Sheidley B (2001) Genetics of autism: complex aetiology for a heterogeneous disorder. Nat Rev Genet 2(12):943–955
Fombonne E (2003) Epidemiological surveys of autism and other pervasive developmental disorders: an update. J Autism Dev Disord 33(4):365–382
Hadjixenofontos A, Schmidt MA, Whitehead PL, Konidari I, Hedges DJ, Wright HH, Abramson RK, Menon R, Williams SM, Cuccaro ML, Haines JL, Gilbert JR, Pericak-Vance MA, Martin ER, McCauley JL (2013) Evaluating mitochondrial DNA variation in autism spectrum disorders. Ann Hum Genet 77(1):9–21
Koenig MK (2008) Presentation and diagnosis of mitochondrial disorders in children. Pediatr Neurol 38:305–313
László A, Horváth E, Eck E, Fekete M (1994) Serum serotonin, lactate and pyruvate levels in infantile autistic children. Clin Chim Acta 229(1–2):205–207
Lerman-Sagie T, Leshinsky-Silver E, Watemberg N, Lev D (2004) Should autistic children be evaluated for mitochondrial disorders? J Child Neurol 19(5):379–381
Ming X, Brimacombe M, Wagner GC (2007) Prevalence of motor impairment in autism spectrum disorders. Brain Dev 29:565–570
MMWR (2009; 58(No. SS-10) CDC. Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, United States, 2006
Munnich A, Rustin P (2001) Clinical spectrum and diagnosis of mitochondrial disorders. Am J Med Genet 106(1):4–17
Munoz A, Mateos F, Simou R, Garcia-Silva MT, Cabello S, Arenas J (1999) Mitochondrial diseases in children: neuroradiological and clinical features in 17 patients. Neuroradiology 41:920–928
Napoli E, Wong S, Giulivi C (2013) Evidence of reactive oxygen species-mediated damage to mitochondrial DNA in children with typical autism. Mol Autism 4(1):2
Oliveira G, Diogo L, Grazina M, Garcia P, Ataíde A, Marques C, Miguel T, Borges L, Vicente AM, Oliveira CR (2005) Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Dev Med Child Neurol 47:185–189
Rossignol DA, Bradstreet JJ (2008) Evidence of mitochondrial dysfunction in autism and implications for treatment. A J Biochem Biotechnol 4(2):208–217
Rossignol DA, Frye RE (2011) Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 17(3):290–314
Saneto RP, Friedman SD, Shaw DW (2008) Neuroimaging of mitochondrial disease. Mitochondrion 8(5–6):396–413
Serajee FJ, Zhang H, Huq AHMM (2006) Prevalence of common mitochondrial point mutations in autism. Neuropediatrics 37(suppl 1):S127
Skladal D, Halliday J, Thorburn DR (2003) Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain 126:1905–1912
Tuchman R, Rapin I (2002) Epilepsy in autism. Lancet Neurol 1(6):352–358
Valanne L, Ketonen L, Majander A, Suomalainen A, Pihko H (1998) Neuroradiologic findings in children with mitochondrial disorders. AJNR Am J Neuroradiol 19:369–377
Vilarinho L, Chorão R, Cardoso ML, Rocha H, Nogueira C, Santorelli FM (1999) The ND1 T3308C mutation may be a mtDNA polymorphism: report of two Portuguese patients. J Inher Metab Dis 22:90–91
Volkmar FR, Pauls D (2003) Autism. Lancet 362:1133–1141
Weissman JR, Kelley RI, Bauman ML, Cohen BH, Murray KF, Mitchell RL, Kern RL, Natowicz MR (2008) Mitochondrial disease in autism spectrum disorder patients: a cohort analysis. PLoS One 3(11):e3815
WHO Multicentre Growth Reference Study Group (2006) WHO motor development study: windows of achievement for six gross motor development milestones. Acta Paediatr Suppl 450:86–95
Wolf NI, Smeitink JA (2002) Mitochondrial disorders: a proposal for consensus diagnostic criteria in infants and children. Neurology 59(9):1402–1405
Zeviani M, Carelli V (2007) Mitochondrial disorders. Curr Opin Neurol 20(5):564
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Guevara-Campos, J., González-Guevara, L., Puig-Alcaraz, C. et al. Autism spectrum disorders associated to a deficiency of the enzymes of the mitochondrial respiratory chain. Metab Brain Dis 28, 605–612 (2013). https://doi.org/10.1007/s11011-013-9419-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-013-9419-x