Biological Trace Element Research

, Volume 188, Issue 1, pp 230–238 | Cite as

Hair Mineral and Trace Element Content in Children with Down’s Syndrome

  • Andrey R. Grabeklis
  • Anatoly V. SkalnyEmail author
  • Anastasia A. Skalnaya
  • Irina V. Zhegalova
  • Svetlana V. Notova
  • Anna L. Mazaletskaya
  • Margarita G. Skalnaya
  • Alexey A. Tinkov


The objective of the present study was to assess the level of minerals and trace elements in 40 children with Down’s syndrome and 40 controls aged 1–2 years old. Hair mineral and trace element analysis was performed using inductively coupled plasma mass spectrometry. The obtained data demonstrate that hair levels of Mg, P, I, Cr, Si, Zn, and Pb in Down’s syndrome patients exceeded the respective control values by 36, 36, 93, 57, 45, 28, and 54%, whereas hair mercury was more than twofold lower in children with Down’s syndrome. The observed difference in the levels of trace elements was age-dependent. In particular, in 1-year-olds, major differences were observed for essential elements (Cr, Si, Zn), whereas in 2-year-olds—for toxic elements (Hg, Pb). At the same time, hair P levels in Down’s syndrome patients were 14 and 35% higher at the age of 1 and 2 years in comparison to the respective controls. Multiple regression analysis demonstrated that a model incorporating all elements, being characterized by a significant group difference, accounted for 42.5% of status variability. At the same time, only hair phosphorus was significantly interrelated with Down’s syndrome status (β = 0.478; p < 0.001). Principal component analysis (PCA) used As, Ca, Cr, Fe, Hg, I, Mg, P, Pb, Se, Si, Sn, and Zn as predictors, with the resulting R2 = 0.559. The OPLS-DA models also separated between Down’s and health control groups. Therefore, 1–2-year-old patients with Down’s syndrome are characterized by significant alterations of mineral and trace element status.


Trisomy 21 Phosphorus Mercury Metals Hair 



The current investigation is supported by the Russian Foundation for Basic Research within project no. 18-013-01026.

Compliance with Ethical Standards

The present study was performed in agreement with the ethical standards set in the Declaration of Helsinki (1964) and its later amendments. The protocol of the investigation was approved by the Institutional Ethics Committee (Yaroslavl State University, Yaroslavl, Russia). Informed consent was obtained from the parents, who were informed about the study, its objectives, and methods. All clinical procedures (examination, sampling) were performed in the presence of parents.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Dierssen M (2012) Down syndrome: the brain in trisomic mode. Nat Rev Neurosci 13:844–858CrossRefGoogle Scholar
  2. 2.
    Loane M, Morris JK, Addor M-C, Arriola L, Budd J, Doray B, Garne E, Gatt M, Haeusler M, Khoshnood B (2013) Twenty-year trends in the prevalence of down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening. Eur J Hum Genet 21:27–33CrossRefGoogle Scholar
  3. 3.
    Grammatikopoulou MG, Manai A, Tsigga M, Tsiligiroglou-Fachantidou A, Galli-Tsinopoulou A, Zakas A (2008) Nutrient intake and anthropometry in children and adolescents with Down syndrome—a preliminary study. Dev Neurorehabil 11:260–267CrossRefGoogle Scholar
  4. 4.
    Roizen NJ, Patterson D (2003) Down’s syndrome. Lancet 361:1281–1289CrossRefGoogle Scholar
  5. 5.
    Asim A, Kumar A, Muthuswamy S, Jain S, Agarwal S (2015) Down syndrome: an insight of the disease. J Biomed Sci 22:41CrossRefGoogle Scholar
  6. 6.
    Ram G, Chinen J (2011) Infections and immunodeficiency in Down syndrome. Clin Exp Immunol 164:9–16CrossRefGoogle Scholar
  7. 7.
    Irving CA, Chaudhari MP (2012) Cardiovascular abnormalities in Down’s syndrome: spectrum, management and survival over 22 years. Arch Dis Child 97:326–330CrossRefGoogle Scholar
  8. 8.
    Sobey CG, Judkins CP, Sundararajan V, Phan TG, Drummond GR, Srikanth VK (2015) Risk of major cardiovascular events in people with Down syndrome. PLoS One 10:e0137093CrossRefGoogle Scholar
  9. 9.
    Perluigi M, Di Domenico F, Buttterfield DA (2014) Unraveling the complexity of neurodegeneration in brains of subjects with Down syndrome: insights from proteomics. Proteomics Clin Appl 8:73–85CrossRefGoogle Scholar
  10. 10.
    Uppal H, Chandran S, Potluri R (2015) Risk factors for mortality in Down syndrome. J Intellect Disabil Res 59:873–881CrossRefGoogle Scholar
  11. 11.
    Melville C, Cooper SA, McGrother C, Thorp C, Collacott R (2005) Obesity in adults with Down syndrome: a case–control study. J Intellect Disabil Res 49:125–133CrossRefGoogle Scholar
  12. 12.
    Cohen WI Current dilemmas in Down syndrome clinical care: celiac disease, thyroid disorders, and atlanto-axial instability. In: Am J Med Genet C: Semin Med Genet, 2006. vol 3. Wiley Online Library, pp 141–148, 142CGoogle Scholar
  13. 13.
    Samarkandy MM, Mohamed BA, Al-Hamdan AA (2012) Nutritional assessment and obesity in Down syndrome children and their siblings in Saudi Arabia. Saudi Med J 33:1216–1221Google Scholar
  14. 14.
    Gąssowska M, Baranowska-Bosiacka I, Moczydłowska J, Tarnowski M, Pilutin A, Gutowska I, Strużyńska L, Chlubek D, Adamczyk A (2016) Perinatal exposure to lead (Pb) promotes Tau phosphorylation in the rat brain in a GSK-3β and CDK5 dependent manner: relevance to neurological disorders. Toxicology 347:17–28CrossRefGoogle Scholar
  15. 15.
    Saghazadeh A, Mahmoudi M, Ashkezari AD, Rezaie NO, Rezaei N (2017) Systematic review and meta-analysis shows a specific micronutrient profile in people with Down syndrome: lower blood calcium, selenium and zinc, higher red blood cell copper and zinc, and higher salivary calcium and sodium. PLoS One 12(4):e0175437CrossRefGoogle Scholar
  16. 16.
    Malakooti N, Pritchard MA, Adlard PA, Finkelstein DI (2014) Role of metal ions in the cognitive decline of Down syndrome. Front Aging Neurosci 6:136CrossRefGoogle Scholar
  17. 17.
    Yenigun A, Ozkinay F, Cogulu O, Coker C, Cetiner N, Ozden G, Aksu O, Ozkinay C (2004) Hair zinc level in Down syndrome. Downs Syndr Res Pract 9(2):53–57CrossRefGoogle Scholar
  18. 18.
    Gargi P, Kr CA, Madhusnata D (2015) Arsenic may play an environmental risk factor to give birth a down syndrome child. Open J Adv Drug Deliv 3:64–71Google Scholar
  19. 19.
    El-Saeed GS, Abdel Maksoud SA, Bassyouni HT, Raafat J, Agybi MH, Wahby AA, Aly HM (2016) Mercury toxicity and DNA damage in patients with Down syndrome. Med Res J 15:22–26CrossRefGoogle Scholar
  20. 20.
    Kosanovic M, Jokanovic M (2011) Quantitative analysis of toxic and essential elements in human hair. Clinical validity of results. Environ Monit Assess 174:635–643CrossRefGoogle Scholar
  21. 21.
    Lockwood CJ, Lynch L, Ghidini A, Lapinski R, Berkowitz G, Thayer B, Miller WA (1993) The effect of fetal gender on the prediction of Down syndrome by means of maternal serum α-fetoprotein and ultrasonographic parameters. Am J Obstet Gynecol 169:1190–1197CrossRefGoogle Scholar
  22. 22.
    LeBlanc A, Dumas P, Lefebvre L (1999) Trace element content of commercial shampoos: impact on trace element levels in hair. Sci Total Environ 229(1–2):121–124CrossRefGoogle Scholar
  23. 23.
    Zhao L-J, Ren T, Zhong R-G (2012) Determination of lead in human hair by high resolution continuum source graphite furnace atomic absorption spectrometry with microwave digestion and solid sampling. Anal Lett 45(16):2467–2481CrossRefGoogle Scholar
  24. 24.
    Skalny AV, Skalnaya MG, Grabeklis AR, Zhegalova IV, Serebryansky EP, Demidov VA, Salnikova EV, Uzhentseva MS, Lobanova YN, Skalny AA (2018) Interactive effects of age and gender on levels of toxic and potentially toxic metals in children hair in different urban environments. Int J Environ Anal Chem:1–16Google Scholar
  25. 25.
    Skalny AV, Skalnaya MG, Tinkov AA, Serebryansky EP, Demidov VA, Lobanova YN, Grabeklis AR, Berezkina ES, Gryazeva IV, Skalny AA (2015) Hair concentration of essential trace elements in adult non-exposed Russian population. Environ Monit Assess 187:677CrossRefGoogle Scholar
  26. 26.
    Gentleman R (2008) R programming for bioinformatics. Chapman and Hall/CRCGoogle Scholar
  27. 27.
    Barlow P, Sylvester P, Dickerson J (1981) Hair trace metal levels in Down syndrome patients. J Intellect Disabil Res 25:161–168CrossRefGoogle Scholar
  28. 28.
    Anneren G, Gebre-Medhin M (1987) Trace elements and transport proteins in serum of children with Down syndrome and of healthy siblings living in the same environment. Hum Nutr Clin Nutr 41:291–299Google Scholar
  29. 29.
    Kędziora J, Witas H, Bartosz G, Leyko W, Jeske J, Rożynkowa D (1978) Down syndrome—transferrin parallels plasma iron changes. Experientia 34(6):712–713CrossRefGoogle Scholar
  30. 30.
    Farrar G, Blair J, Altmann P, Welch S, Wychrij O, Ghose B, Lejeune J, Corbett J, Prasher V (1990) Defective gallium-transferrin binding in Alzheimer disease and Down syndrome: possible mechanism for accumulation of aluminium in brain. Lancet 335(8692):747–750CrossRefGoogle Scholar
  31. 31.
    Hodgkins PS, Prasher V, Farrar G, Armstrong R, Sturman S, Corbett J, Blair JA (1993) Reduced transferrin binding in Down syndrome: a route to senile plaque formation and dementia. Neuroreport 5(1):21–24CrossRefGoogle Scholar
  32. 32.
    Cutress T (1972) Composition, flow-rate and pH of mixed and parotid salivas from trisomic 21 and other mentally retarded subjects. Arch Oral Biol 17:1081–1094CrossRefGoogle Scholar
  33. 33.
    Baptista F, Varela A, Sardinha LB (2005) Bone mineral mass in males and females with and without Down syndrome. Osteoporos Int 16:380–388CrossRefGoogle Scholar
  34. 34.
    McKelvey K, Fowler T, Akel N, Kelsay J, Gaddy D, Wenger G, Suva L (2013) Low bone turnover and low bone density in a cohort of adults with Down syndrome. Osteoporos Int 24:1333–1338CrossRefGoogle Scholar
  35. 35.
    Blazek JD, Gaddy A, Meyer R, Roper RJ, Li J (2011) Disruption of bone development and homeostasis by trisomy in Ts65Dn Down syndrome mice. Bone 48(2):275–280CrossRefGoogle Scholar
  36. 36.
    Stagi S, Lapi E, Romano S, Bargiacchi S, Brambilla A, Giglio S, Seminara S, de Martino M (2015) Determinants of vitamin d levels in children and adolescents with Down syndrome. Int J Endocrinol 2015:896758CrossRefGoogle Scholar
  37. 37.
    Hruska K (2017) Overview of phosphorus homeostasis. In: Clinical aspects of natural and added phosphorus in foods. Springer, pp 11–28Google Scholar
  38. 38.
    Li T, Xie Y, Bowe B, Xian H, Al-Aly Z (2017) Serum phosphorus levels and risk of incident dementia. PLoS One 12(2):e0171377CrossRefGoogle Scholar
  39. 39.
    Siritapetawee J, Pattanasiriwisawa W, Sirithepthawee U (2010) Trace element analysis of hairs in patients with dementia. J Synchrotron Radiat 17(2):268–272CrossRefGoogle Scholar
  40. 40.
    Baltaci AK, Yuce K (2017) Zinc Transporter Proteins. Neurochem Res:1–14Google Scholar
  41. 41.
    Baltaci AK, Yuce K, Mogulkoc R (2018) Zinc metabolism and metallothioneins. Biol Trace Elem Res 183(1):22–31CrossRefGoogle Scholar
  42. 42.
    Marques RC, de Sousa AF, do Monte SJH, Oliveira FE, do Nascimento Nogueira N, do Nascimento Marreiro D (2007) Zinc nutritional status in adolescents with Down syndrome. Biol Trace Elem Res 120:11–18CrossRefGoogle Scholar
  43. 43.
    Lima AS, Cardoso BR, Cozzolino SF (2010) Nutritional status of zinc in children with Down syndrome. Biol Trace Elem Res 133:20–28CrossRefGoogle Scholar
  44. 44.
    Licastro F, Mariani RA, Faldella G, Carpenè E, Guidicini G, Rangoni A, Grilli T, Bazzocchi G (2001) Immune-endocrine status and coeliac disease in children with Down’s syndrome: relationships with zinc and cognitive efficiency. Brain Res Bull 55:313–317CrossRefGoogle Scholar
  45. 45.
    Magenis ML, Machado AG, Bongiolo AM, MAd S, Castro K, Perry IDS (2018) Dietary practices of children and adolescents with Down syndrome. J Intellect Disabil 22:125–134CrossRefGoogle Scholar
  46. 46.
    Nourmohammadi I, Raiei F (2003) Zinc hair concentration in children suffering from Down syndrome, cerebral palsy, macrocephaly and hydrocephaly. Iran J Psychiatry Clin Psychol 8:83–88Google Scholar
  47. 47.
    Koc ER, Ilhan A, Aytürk Z, Acar B, Gürler M, Altuntaş A, Karapirli M, Bodur AS (2015) A comparison of hair and serum trace elements in patients with Alzheimer disease and healthy participants. Turk J Med Sci 45:1034–1039CrossRefGoogle Scholar
  48. 48.
    Soto-Quintana M, Alvarez-Nava F, Rojas-Atencio A, Granadillo V, Fernandez D, Ocando A, López E, Fulcado W (2003) Diminished zinc plasma concentrations and alterations in the number of lymphocyte subpopulations in Down’s syndrome patients. Investig Clin 44:51–60Google Scholar
  49. 49.
    Chiricolo M, Musa AR, Monti D, Zannoti M, Franceschi C (1993) Enhanced DNA repair in lymphocytes of Down syndrome patients: the influence of zinc nutritional supplementation. Mutat Res 295:105–111CrossRefGoogle Scholar
  50. 50.
    Romano C, Pettinato R, Ragusa L, Barone C, Alberti A, Failla P (2002) Is there a relationship between zinc and the peculiar comorbidities of Down syndrome? Downs Syndr Res Pract 8:25–28CrossRefGoogle Scholar
  51. 51.
    Pierce MJ, LaFranchi SH, Pinter JD (2017) Characterization of thyroid abnormalities in a large cohort of children with Down syndrome. Horm Res Paediatr 87:170–178CrossRefGoogle Scholar
  52. 52.
    Tinkov AA, Popova EV, Polyakova VS, Kwan OV, Skalny AV, Nikonorov AA (2015) Adipose tissue chromium and vanadium disbalance in high-fat fed Wistar rats. J Trace Elem Med Biol 29:176–181CrossRefGoogle Scholar
  53. 53.
    Lott IT (2012) Neurological phenotypes for Down syndrome across the life span. In: Prog Brain Res, vol 197. Elsevier, pp 101–121Google Scholar
  54. 54.
    Villani E, Onder G, Carfì A, Di Segni C, Raimondo S, Silvestrini A, Meucci E, Mancini A (2016) Thyroid function and its implications in oxidative stress influencing the pathogenesis of osteoporosis in adults with Down syndrome: a cohort study. Horm Metab Res 48:565–570CrossRefGoogle Scholar
  55. 55.
    Heinitz MF (2005) Alzheimer’s disease and trace elements: chromium and zinc. J Orthomol Med 20(2):89–92Google Scholar
  56. 56.
    Krikorian R, Eliassen JC, Boespflug EL, Nash TA, Shidler MD (2010) Improved cognitive-cerebral function in older adults with chromium supplementation. Nutr Neurosci 13:116–122CrossRefGoogle Scholar
  57. 57.
    Vink R (2016) Magnesium in the CNS: recent advances and developments. Magnes Res 29:95–101Google Scholar
  58. 58.
    Siqueira WL, de Oliveira E, Mustacchi Z, Nicolau J (2004) Electrolyte concentrations in saliva of children aged 6-10 years with Down syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 98:76–79CrossRefGoogle Scholar
  59. 59.
    Kadrabová J, Madáriĉ A, Šustrová M, Ginter E (1996) Changed serum trace element profile in Down’s syndrome. Biol Trace Elem Res 54:201–206CrossRefGoogle Scholar
  60. 60.
    Anneren G, Johansson E, Lindh U (1985) Trace element profiles in individual blood cells from patients with Down’s syndrome. Acta Paediatr 74:259–263CrossRefGoogle Scholar
  61. 61.
    Moore PB, Edwardson JA, Ferrier IN, Taylor GA, Lett D, Tyrer SP, Day JP, King SJ, Lilley JS (1997) Gastrointestinal absorption of aluminum is increased in Down’s syndrome. Biol Psychiatry 41:488–492CrossRefGoogle Scholar
  62. 62.
    Domingo JL, Gómez M, Colomina MT (2011) Oral silicon supplementation: an effective therapy for preventing oral aluminum absorption and retention in mammals. Nutr Rev 69:41–51CrossRefGoogle Scholar
  63. 63.
    Davenward S, Bentham P, Wright J, Crome P, Job D, Polwart A, Exley C (2013) Silicon-rich mineral water as a non-invasive test of the ‘aluminum hypothesis’ in Alzheimer’s disease. J Alzheimers Dis 33:423–430CrossRefGoogle Scholar
  64. 64.
    Exley C (2017) Aluminum should now be considered a primary etiological factor in Alzheimer’s disease. J Alzheimers Dis Rep 1:23–25CrossRefGoogle Scholar
  65. 65.
    Kobayashi S, Fujiwara S, Arimoto S, Koide H, Fukuda J, Shimode K, Yamaguchi S, Okada K, Tsunematsu T (1989) Hair aluminium in normal aged and senile dementia of Alzheimer type. Prog Clin Biol Res 317:1095–1109Google Scholar
  66. 66.
    Marlowe M, Moon C, Errera J, Stellern J (1983) Hair mineral content as a predictor of mental retardation. Orthomol Psych 12:26–33Google Scholar
  67. 67.
    Kern JK, Grannemann BD, Trivedi MH, Adams JB (2007) Sulfhydryl-reactive metals in autism. J Toxicol Environ Health A 70:715–721CrossRefGoogle Scholar
  68. 68.
    Kern JK, Geier DA, Sykes LK, Haley BE, Geier MR (2016) The relationship between mercury and autism: a comprehensive review and discussion. J Trace Elem Med Biol 37:8–24CrossRefGoogle Scholar
  69. 69.
    Oxelgren UW, Myrelid Å, Annerén G, Ekstam B, Göransson C, Holmbom A, Isaksson A, Åberg M, Gustafsson J, Fernell E (2017) Prevalence of autism and attention-deficit–hyperactivity disorder in Down syndrome: a population-based study. Dev Med Child Neurol 59(3):276–283CrossRefGoogle Scholar
  70. 70.
    Mutter J, Curth A, Naumann J, Deth R, Walach H (2010) Does inorganic mercury play a role in Alzheimer’s disease? A systematic review and an integrated molecular mechanism. J Alzheimers Dis 22:357–374CrossRefGoogle Scholar
  71. 71.
    Koseoglu E, Koseoglu R, Kendirci M, Saraymen R, Saraymen B (2017) Trace metal concentrations in hair and nails from Alzheimer’s disease patients: relations with clinical severity. J Trace Elem Med Biol 39:124–128CrossRefGoogle Scholar
  72. 72.
    McDermott S, Wu J, Cai B, Lawson A, Aelion CM (2011) Probability of intellectual disability is associated with soil concentrations of arsenic and lead. Chemosphere 84(1):31–38CrossRefGoogle Scholar
  73. 73.
    Bihaqi SW, Huang H, Wu J, Zawia NH (2011) Infant exposure to lead (Pb) and epigenetic modifications in the aging primate brain: implications for Alzheimer’s disease. J Alzheimers Dis 27(4):819–833CrossRefGoogle Scholar
  74. 74.
    Ryoo S-R, Jeong HK, Radnaabazar C, Yoo J-J, Cho H-J, Lee H-W, Kim I-S, Cheon Y-H, Ahn YS, Chung S-H (2007) DYRK1A-mediated hyperphosphorylation of Tau A functional link between Down syndrome and Alzheimer disease. J Biol Chem 282:34850–34857CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Andrey R. Grabeklis
    • 1
    • 2
  • Anatoly V. Skalny
    • 1
    • 2
    • 3
    Email author
  • Anastasia A. Skalnaya
    • 4
  • Irina V. Zhegalova
    • 2
  • Svetlana V. Notova
    • 5
    • 6
  • Anna L. Mazaletskaya
    • 1
  • Margarita G. Skalnaya
    • 1
    • 2
  • Alexey A. Tinkov
    • 1
    • 2
  1. 1.Yaroslavl State UniversityYaroslavlRussia
  2. 2.Peoples’ Friendship University of Russia (RUDN University)MoscowRussian Federation
  3. 3.All-Russian Research Institute of Medicinal and Aromatic Plants (VILAR)MoscowRussia
  4. 4.Lomonosov Moscow State UniversityMoscowRussia
  5. 5.Orenburg State UniversityOrenburgRussia
  6. 6.Federal Research Centre of Biological Systems and Agro-technologies of the Russian Academy of SciencesOrenburgRussia

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