Hyperhomocysteinemia among Omani autistic children: a case-control study

• Authors: Amanat Ali , Mostafa I. Waly , Yahya M. Al-Farsi , Musthafa M. Essa , Marwan M. Al-Sharbati , Richard C. Deth
• Languages of publication: EN

Abstracts

EN

High serum homocysteine (Hcy) level is regarded as an indicator for impairment of folate-dependent methionine cycle and is associated with oxidative stress. In a case control study, we evaluated eighty 3-5 years old Omani children (40 diagnosed with Autism Spectrum Disorder and 40 their age and gender matched controls) for their fasting serum homocysteine levels as a biomarker of Autism Spectrum Disorder (ASD). Serum folate and vitamin B12 status were also evaluated. The serum homocysteine was measured using an enzyme immunoassay (EIA) technique whereas folate and vitamin B12 were measured using an automated random access immune-assay system. The results indicated that mean serum Hcy levels were significantly (P < 0.05) higher in autistic children (20.1 ± 3.3 µmol/L) as compared to controls (9.64 ± 2.1 µmol/L). Significantly (P < 0.05) lower serum folate (1.8 ± 0.4 µg/L) and vitamin B12 (191.1 ± 0.9 pg/mL) levels were observed in autistic children as compared to controls (6.1 ± 0.6 µg/L and 288.9 ± 1.3 pg/mL, respectively). The levels of homocysteine in autistic children were also much higher as compared to normal reference values (5-15 µmol/L). The results suggest that high fasting serum homocysteine and low folate and vitamin B12 levels could be used as clinical biomarkers for an early diagnosis and management of ASD.

Keywords

EN

autistic children; vitamin B12; Oman; folate; serum homocysteine

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2011
• Volume: 58
• Issue: 4
• Pages: 547-551

Dates

published

2011

received

2011-05-10

revised

2011-11-25

accepted

2011-12-11

(unknown)

2011-12-20

Contributors

author

Amanat Ali

• Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman

author

Mostafa I. Waly

• Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman

author

Yahya M. Al-Farsi

• Family Medicine and Public Health Department, College of Medicine and Health Sciences, Sultan Qaboos University, Oman

author

Musthafa M. Essa

• Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Oman

author

Marwan M. Al-Sharbati

• Behavioural Medicine Department, College of Medicine and Health Sciences, Sultan Qaboos University, Oman

author

Richard C. Deth

• Pharmacology Department, Bouve College of Health Sciences, Northeastern University, Boston, MA 02115, USA

References

• Adams JB, Baral M, Geis E, Mitchell J, Ingram J, Hensley A, Zappia I, Newmark S, Gehn E, Rubin RA, Mitchell K, Bradstreet J, El-Dahr JM (2009) The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicol 2009: Article ID 532640, 7 pages, Doi:10.1155/2009/532640.
• Ahearn WH, Castine T, Nault K, Green G (2001) An assessment of food acceptance in children with autism or pervasive developmental disorder not otherwise specified. J Autism Dev Disord 31: 505- 511.
• Al-Farsi MY, Al-Sharbati MM, Al-Farsi AO, Al-Shafaee SM, Brooks RD, Waly IM (2011) Brief Report: Prevalence of Autistic Spectrum Disorders in the Sultanate of Oman. J Autism Dev Disord. 41: 821-825.
• Al-Gadani Y, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to oxidative stress in Saudi autistic children. Clin Biochem 42: 1032-1040.
• Al-Mosalem OA, El-Ansary A, Attas O, Al-Ayadhi L (2009) Metabolic biomarkers related to energy metabolism in in Saudi autistic children. Clin Biochem 42: 949-957.
• American Psychiatric Association, APA (2000) Diagnostic criteria for autistic disorder. In: Diagnostic and statistical manual of maternal disorders (Fourth Edition text revision (DSM-IV-TR). American Psychiatric Association, Washington, DC, USA, pp. 75.
• Bernard S, Enayati A, Roger H, Binstock T, Redwood L (2002) The role of mercury in the pathogenesis of autism. Mol Psychiatry 7: S42-S43.
• Blaylock RL (2008) A possible central mechanism in autism spectrum disorders, part 1. Altern Ther Health Med 14: 46-53.
• Blaylock RL (2009a) A possible central mechanism in autism spectrum disorders, part 2. immunoexcitotoxicity. Altern Ther Health Med 15(1): 60-67.
• Blaylock RL (2009b) A possible central mechanism in autism spectrum disorders, part 3: the role of excitotoxin food additives and the synergistic effects of other environmental toxins. Altern Ther Health Med 15(2): 56-60.
• Boris M, Goldblatt A, Galanko J, James JM (2004) Association of MTHFR Gene Variants with Autism. J Am Phys Surg 1: 106-108.
• Buehler MR (2011) A proposed mechanism for autism: an aberrant neuroimmune response manifested as a psychiatric disorder. Med Hypotheses [Epub ahead of print].
• Chauhan A, Chauhan V (2006) Oxidative stress in autism. Pathophysiology 13: 171-181.
• Chen CS, Chou MC, Yeh YC, Yang YH, Lai CL, Yen CF, Liu CK, Liao YC (2010) Plasma homocysteine levels and major depressive disorders in Alzheimer disease. Am J Geriatr Psychiatry 18: 1045-1048.
• Daniels AM, Rosenberg RE, Anderson C, Law JK, Marvin AR, Law PA (2011) Verification of Parent-Report of Child Autism Spectrum Disorder Diagnosis to a Web-Based Autism Registry. J Autism Dev Disord. DOI.10.1007/s10803-011-1236-7.
• Dhonukshe-Rutten RA, de Vries JH, de Bree A, van der Put N, van Staveren WA, de Groot LC (2009) Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations. Eur J Clin Nutr 63: 18-30.
• El-Ansary AK, Bacha AG, Al-Ayahdi L (2011) Plasma fatty acids as diagnostic markers in autistic patients from Saudi. Lipids Health Dis 10: 62. doi:10.1186/1476-511X-10-62.
• Frantzen F, Faaren AL, Alfheim I, Nordhei AK (1998) Enzyme conversion immunoassay for determining total homocysteine in plasma or serum. Clin Chem 44: 311-316.
• Herrmann W, Herrmann M, Obeid R (2007) Hyperhomocysteinaemia: a critical review of old and new aspects. Curr Drug Metab 8: 17-31.
• Herrmann W, Obeid R (2011) Homocysteine: a biomarker in neurodegenerative diseases. Clin Chem Lab Med 49: 435-441.
• Hoţoleanu C, Porojan-Iuga M, Rusu ML, Andercou A (2007) Hyperhomocysteinemia: clinical and therapeutical involvement in venous thrombosis. Rom J Intern Med 45: 159-64.
• Humphrey LL, Fu R, Roger K, Freeman M, Helfand M (2008) Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc 83: 1203-1212.
• Ientile R, Curro' M, Ferlazzo N, Condello S, Caccamo D, Pisani F (2010) Homocysteine, vitamin determinants and neurological diseases. Front Biosci (Schol Ed) 2: 359-372.
• James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, Neubrander JA (2004) Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism Am J Clin Nutr 80: 1611-1617.
• James SJ, Melnyk S, Jernigan S, Hubanks A, Rose S, Gaylor DW (2008) Abnormal transmethylation/transsulfuration metabolism and DNA hypomethylation among parents of children with autism. J Autism Dev Disord 38: 1976.
• James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW (2009) Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am J Clin Nutr 89: 425-30.
• Kaluzna-Czaplinska J, Michalska M, Socha E, Blaszczyk S, Rozetti-Szymariska A, Rynkowski J (2009) Nutritional deficiencies in children for example of autistic children. Nowa Pediatria 4: 94-100.
• Kaluzna-Czaplinska J, Michalska M, Rynkowski J (2011a) Homocysteine level in urine of autistic and healthy children. Acta Biochim Polon 58: 31-34.
• Kaluzna-Czaplinska J, Michalska M, Rynkowski J (2011b) Vitamin supplementation reduces the levels of homocysteine in the urine of autistic children. Nutr Res 31: 318-321.
• Keller F, Persico AM (2007) The neurobiological context of autism. Mol Neurobiol 28: 1-22.
• Kern JK, Geier DA, Adams JB, Geier MR (2010) A biomarker of mercury body-burden correlated with diagnostic domain specific clinical symptoms of autism specrum disorder. Biometals 23: 1043-1051.
• Levenson VV (2010) DNA methylation as a universal biomarker. Expert Rev Mol Diagn 10: 481-488. .
• Lubinska M, Kazimierska E, Sworczak K (2006) Hyperhomocysteinemia as a new risk factor for different disease. Adv Clin Exp Med 15: 897-903.
• Miller AM, Kelly GS (1996) Methionine and homocysteine metabolism and the nutritional prevention of certain birth defects and complications of pregnancy. Altern Med Rev 4: 220-235.
• Miller AL (2003) The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev 8: 7-19.
• Moretti P, Sahoo T, Hyland K, Bottiglieri T, Peters S, del Gaudio D, Roa B, Curry S, Zhu H, Finnell RH, Neul JL, Ramaekers VT, Blau N, Bacino CA, Miller G, Scaglia F (2005) Cerebral folate deficiency with developmental delay, autism, and response to folinic acid. Neurology 64: 1088-1090.
• Muntjewerff JW, van der Put N, Eskes T, Ellenbroek B, Steegers E, Blom H, Zitman F (2003) Homocysteine metabolism and B-vitamins in schizophrenic patients: low plasma folate as a possible independent risk factor for schizophrenia. Psychiatry Res 121: 1-9.
• Newton LA, Sandhu K, Livingstone C, Leslie R, Davis J. (2010) Clinical diagnostics for homocysteine: a rogue amino acid? Expert Rev Mol Diagn 10: 489-500.
• Paşca SP, Nemeş B, Vlase L, Gagyi CE, Dronca E, Miu AC, Dronca M (2006) High levels of homocysteine and low serum paraoxonase 1 arylesterase activity in children with autism. Life Sci 78: 2244-2248.
• Paşca SP, Dronca E, Kaucsar T, Craciun EC, Endreffy E, Ferencz BK (2008) One carbon metabolism disturbances and C677T MTHFR gene polymorphism in children with autism spectrum disorders. J Cell Mol Med 13: 4229-4238.
• Paul C, William KE, Riegel K, Gibbons B (2007) Combining repeated taste exposure and escape prevention: an intervention for the treatment of extreme food selectivity. Appetite 49: 708-711.
• Quillard M, Berthe MC, Sauger F, Lavoinne A (2003) Plasma determination of homocysteine on CPC Immulite 2000: comparison with determination on IMX Abbott. Ann Biol Clin (Paris) 61: 699-704.
• Reading R (2008) Autism spectrum disorders: clinical and research frontiers. Child Care Health Dev. 34: 697-708.
• Remacha AF, Souto JC, Piñana JL, Sardà MP, Queraltó JM, Martí-Fabregas J, García-Moll X, Férnandez C, Rodriguez A, Cuesta J (2011) Vitamin B12 deficiency, hyperhomocysteinemia and thrombosis: a case and control study. Int J Hematol 93: 458-64.
• Ryan BM, Weir DG (2001) relevance of folate metabolism in the pathogenesis of colorectal cancer. J lab Clin Med 138: 164-176.
• Santangelo SL, Tsatsanis K (2005) What is known about autism: genes, brain, and behavior? Am J Pharmacogenomics 5: 71-92.
• dos Santos PA, Longo D, Brandalize AP, Schuler-Faccini L (2010) MTHFR C677T is not a risk factor for autism spectrum disorders in South Brazil. Psychiatr Genet 20: 187-189.
• Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA (2002) Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 346: 476-483.
• Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ (2006) Modern Nutrition in Health and Disease, 10th edn, pp 550-552. Lippincott Williams & Wilkins, A Wolter Kulwer Company, Baltimore, Maryland, USA.
• Snedecor G, Cochran G (1989) Statistical Methods, 8th ed, Iowa State University Press, Iowa, USA.
• Suh JH, Walsh WJ, McGinnis WR, Lewis A, Ames BN (2008) Altered sulfur amino acid metabolism in immune cells of children diagnosed with autism. Am J Biochem Biotechnol 4: 105-113.
• Towle PO, Visintainer PF, O'Sullivan C, Bryant NE, Busby S (2009) Detecting autism spectrum disorder from early intervention charts: methodology and preliminary findings. J Autism Dev Disord 39: 444-452.
• Tu MC, Huang CW, Chen NC, Chang WN, Lui CC, Chen CF, Chen C , Wang YL, Lin YT, Chang CC (2010) Hyperhomocysteinemia in Alzheimer dementia patients and cognitive decline after 6 months follow-up period. Acta Neurol Taiwan 19: 168-177.
• Waly M, Olteanu H, Banerjee R, Choi SW, Mason JB, Parker BS, Sukumar S, Shim S, Sharma A, Benzecry JM, Power-Charnitsky VA, Deth RC (2004) Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal. Mol Psychiatry 9: 358-370.
• Waskiewicz A, Sygnowska E, Broda G (2010) Dietary intake of vitamin B6, B12 and folate in relation to homocysteine serum concentration in the adult Polish population - WOBASZ Project. Kardiol Pol 68: 275-282.
• Weiser M, Reichenberg A, Werbeloff N, Kleinhaus K, Lubin G, Shmushkevitch M, Caspi A, Malaspina D, Davidson M (2008) Advanced parental age at birth is associated with poorer social functioning in adolescent males: shedding light on a core symptom of schizophrenia and autism. Schizophr Bull 34: 1042-1046.
• Wijsman CA, van Heemst D, Rozing MP, Slagboom PE, Beekman M, de Craen AJ, Maier AB, Westendorp RG, Blom HJ, Mooijaart SP (2011) Homocysteine and familial longevity: the Leiden Longevity Study. PLoS One 6: e17543.
• Xia RR (2011) Effectiveness of nutritional supplements for reducing symptoms in autism-spectrum disorder: a case report. J Altern Complement Med 17: 271-274.