Journal of Pediatric Neurology 2019; 17(06): 199-205
DOI: 10.1055/s-0038-1676633
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Is Metabolic Screening Necessary in Children with Autism Spectrum Disorder? A Mini Review

Maria Gogou
1   Fourth Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece
,
Athanasios Evangeliou
1   Fourth Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, General Hospital Papageorgiou, Thessaloniki, Greece
› Author Affiliations
Funding None.
Further Information

Publication History

21 September 2018

10 November 2018

Publication Date:
21 December 2018 (online)

Abstract

Autism spectrum disorder is a clinically heterogeneous entity with no known specific cause. A variety of inborn errors of metabolism include autistic-like phenotypes in their clinical manifestations. As targeted therapies for many of these errors exist, a question arises whether a routine metabolic screening in all children with autism should be performed. According to current literature, a metabolic workup should not be considered in children with nonsyndromic autism as a first-line investigation. However, detailed cost–benefit analyses are needed to investigate the benefit of a targeted screening of treatable metabolic errors compared with the total financial burden of autism.

 
  • References

  • 1 Park HR, Lee JM, Moon HE. , et al. A short review on the current understanding of autism spectrum disorders. Exp Neurobiol 2016; 25 (01) 1-13
  • 2 Ivanov HY, Stoyanova VK, Popov NT, Vachev TI. Autism spectrum disorder - a complex genetic disorder. Folia Med (Plovdiv) 2015; 57 (01) 19-28
  • 3 de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH. Advancing the understanding of autism disease mechanisms through genetics. Nat Med 2016; 22 (04) 345-361
  • 4 García-Cazorla A. [Neurometabolic diseases: guidance for neuropaediatricians]. Rev Neurol 2008; 47 (Suppl. 01) S55-S63
  • 5 Frye RE, Rossignol DA. Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders. Pediatr Res 2011; 69 (5 Pt 2): 41R-47R
  • 6 Frye RE, Rose S, Slattery J, MacFabe DF. Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome. Microb Ecol Health Dis 2015; 26: 27458
  • 7 Manzi B, Loizzo AL, Giana G, Curatolo P. Autism and metabolic diseases. J Child Neurol 2008; 23 (03) 307-314
  • 8 Schulze A, Hoffmann GF, Bachert P. , et al. Presymptomatic treatment of neonatal guanidinoacetate methyltransferase deficiency. Neurology 2006; 67 (04) 719-721
  • 9 Arias-Dimas A, Vilaseca MA, Artuch R, Ribes A, Campistol J. [Diagnosis and treatment of brain creatine deficiency syndromes] [Article in Spanish]. Rev Neurol 2006; 43 (05) 302-308
  • 10 Görker I, Tüzün U. Autistic-like findings associated with a urea cycle disorder in a 4-year-old girl. J Psychiatry Neurosci 2005; 30 (02) 133-135
  • 11 Jira PE, Wevers RA, de Jong J. , et al. Simvastatin. A new therapeutic approach for Smith-Lemli-Opitz syndrome. J Lipid Res 2000; 41 (08) 1339-1346
  • 12 Adams JB, Audhya T, McDonough-Means S. , et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr 2011; 11: 111
  • 13 Naviaux JC, Wang L, Li K. , et al. Antipurinergic therapy corrects the autism-like features in the fragile X (Fmr1 knockout) mouse model. Mol Autism 2015; 6: 1
  • 14 Frye RE, Slattery J, Delhey L. , et al. Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial. Mol Psychiatry 2018; 23 (02) 247-256
  • 15 Hendren RL, James SJ, Widjaja F, Lawton B, Rosenblatt A, Bent S. Randomized, placebo-controlled trial of methyl B12 for children with autism. J Child Adolesc Psychopharmacol 2016; 26 (09) 774-783
  • 16 Rogers MH, Lwin R, Fairbanks L, Gerritsen B, Gaspar HB. Cognitive and behavioral abnormalities in adenosine deaminase deficient severe combined immunodeficiency. J Pediatr 2001; 139 (01) 44-50
  • 17 Casarano M, Alessandrì MG, Salomons GS. , et al. Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency. JIMD Rep 2012; 2: 119-123
  • 18 Vogel KR, Pearl PL, Theodore WH, McCarter RC, Jakobs C, Gibson KM. Thirty years beyond discovery--clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. J Inherit Metab Dis 2013; 36 (03) 401-410
  • 19 Asato MR, Goldstein AC, Schiff M. Autism and inborn errors of metabolism: how much is enough?. Dev Med Child Neurol 2015; 57 (09) 788-789
  • 20 Hahn A, Neubauer BA. Autism and metabolic disorders-a rational approach [article in German]. Z Kinder Jugendpsychiatr Psychother 2005; 33 (04) 259-271
  • 21 Moss J, Howlin P. Autism spectrum disorders in genetic syndromes: implications for diagnosis, intervention and understanding the wider autism spectrum disorder population. J Intellect Disabil Res 2009; 53 (10) 852-873
  • 22 Schiff M, Delorme R, Benoist JF, Ogier de Baulny H. Should a metabolic work-up be performed in autism? [article in French]. Arch Pediatr 2010; 17 (06) 802-803
  • 23 Schiff M, Benoist JF, Aïssaoui S. , et al. Should metabolic diseases be systematically screened in nonsyndromic autism spectrum disorders?. PLoS One 2011; 6 (07) e21932
  • 24 Isaksen J, Bryn V, Diseth TH, Heiberg A, Schjølberg S, Skjeldal OH. Children with autism spectrum disorders - the importance of medical investigations. Eur J Paediatr Neurol 2013; 17 (01) 68-76
  • 25 Campistol J, Díez-Juan M, Callejón L. , et al. Inborn error metabolic screening in individuals with nonsyndromic autism spectrum disorders. Dev Med Child Neurol 2016; 58 (08) 842-847
  • 26 Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. Cerebral folate receptor autoantibodies in autism spectrum disorder. Mol Psychiatry 2013; 18 (03) 369-381
  • 27 Rossignol DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis. Mol Psychiatry 2012; 17 (03) 290-314
  • 28 Spilioti M, Evangeliou AE, Tramma D. , et al. Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD). Front Hum Neurosci 2013; 7: 858
  • 29 Ghaziuddin M, Al-Owain M. Autism spectrum disorders and inborn errors of metabolism: an update. Pediatr Neurol 2013; 49 (04) 232-236
  • 30 Rumsey RK, Rudser K, Delaney K, Potegal M, Whitley CB, Shapiro E. Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. J Pediatr 2014; 164 (05) 1147-1151.e1
  • 31 Gogou M, Spilioti M, Tramma D, Papadopoulou-Alataki E, Evangeliou A. Succinic semialdehyde dehydrogenase deficiency presenting as autism spectrum disorder. Indian J Pediatr 2016; 83 (09) 1036-1037
  • 32 Adams JB, Audhya T, Geis E. , et al. Comprehensive nutritional and dietary intervention for autism spectrum disorder-a randomized, controlled 12-month trial. Nutrients 2018; 10 (03) E369
  • 33 James SJ, Melnyk S, Jernigan S, Hubanks A, Rose S, Gaylor DW. Abnormal transmethylation/transsulfuration metabolism and DNA hypomethylation among parents of children with autism. J Autism Dev Disord 2008; 38 (10) 1966-1975
  • 34 Rose S, Melnyk S, Pavliv O. , et al. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl Psychiatry 2012; 2: e134
  • 35 James SJ, Rose S, Melnyk S. , et al. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEB J 2009; 23 (08) 2374-2383
  • 36 James SJ, Melnyk S, Fuchs G. , et al. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr 2009; 89 (01) 425-430
  • 37 Frye RE, Melnyk S, Fuchs G. , et al. Effectiveness of methylcobalamin and folinic acid treatment on adaptive behavior in children with autistic disorder is related to glutathione redox status. Autism Res Treat 2013; 2013: 609705
  • 38 Howsmon DP, Vargason T, Rubin RA. , et al. Multivariate techniques enable a biochemical classification of children with autism spectrum disorder versus typically-developing peers: a comparison and validation study. Bioeng Transl Med 2018; 3 (02) 156-165
  • 39 Anwar A, Abruzzo PM, Pasha S. , et al. Advanced glycation endproducts, dityrosine and arginine transporter dysfunction in autism - a source of biomarkers for clinical diagnosis. Mol Autism 2018; 9: 3
  • 40 James SJ, Cutler P, Melnyk S. , et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr 2004; 80 (06) 1611-1617
  • 41 Howsmon DP, Kruger U, Melnyk S, James SJ, Hahn J. Classification and adaptive behavior prediction of children with autism spectrum disorder based upon multivariate data analysis of markers of oxidative stress and DNA methylation. PLOS Comput Biol 2017; 13 (03) e1005385
  • 42 Khemakhem AM, Frye RE, El-Ansary A, Al-Ayadhi L, Bacha AB. Novel biomarkers of metabolic dysfunction is autism spectrum disorder: potential for biological diagnostic markers. Metab Brain Dis 2017; 32 (06) 1983-1997
  • 43 Rose S, Niyazov DM, Rossignol DA, Goldenthal M, Kahler SG, Frye RE. Clinical and molecular characteristics of mitochondrial dysfunction in autism spectrum disorder. Mol Diagn Ther 2018; 22 (05) 571-593
  • 44 Frye RE, Rossignol DA. Treatments for biomedical abnormalities associated with autism spectrum disorder. Front Pediatr 2014; 2: 66
  • 45 Delhey LM, Nur Kilinc E, Yin L. , et al. The effect of mitochondrial supplements on mitochondrial activity in children with autism spectrum disorder. J Clin Med 2017; 6 (02) E18
  • 46 Frye RE, Rose S, Chacko J. , et al. Modulation of mitochondrial function by the microbiome metabolite propionic acid in autism and control cell lines. Transl Psychiatry 2016; 6 (10) e927
  • 47 Children's autism metabolome project (CAMP). Available at: http://www.stemina.com/custom-services/diagnostics/autism/childrens-autism-metabolome-project-camp
  • 48 Horlin C, Falkmer M, Parsons R, Albrecht MA, Falkmer T. The cost of autism spectrum disorders. PLoS One 2014; 9 (09) e106552
  • 49 Ou JJ, Shi LJ, Xun GL. , et al. Employment and financial burden of families with preschool children diagnosed with autism spectrum disorders in urban China: results from a descriptive study. BMC Psychiatry 2015; 15: 3
  • 50 Lavelle TA, Weinstein MC, Newhouse JP, Munir K, Kuhlthau KA, Prosser LA. Economic burden of childhood autism spectrum disorders. Pediatrics 2014; 133 (03) e520-e529
  • 51 Lokhandwala T, Khanna R, West-Strum D. Hospitalization burden among individuals with autism. J Autism Dev Disord 2012; 42 (01) 95-104
  • 52 Leigh JP, Du J. Brief report: forecasting the economic burden of autism in 2015 and 2025 in the United States. J Autism Dev Disord 2015; 45 (12) 4135-4139
  • 53 Järbrink K, McCrone P, Fombonne E, Zandén H, Knapp M. Cost-impact of young adults with high-functioning autistic spectrum disorder. Res Dev Disabil 2007; 28 (01) 94-104