Skip to main content
SpringerLink
Log in

Down Syndrome

  • Chapter
  • First Online:
Metabolism of Human Diseases

Abstract

Down syndrome (DS) or trisomy of chromosome 21 is the most prevalent cause of genetic intellectual disability affecting approximately 1 in 700 live births. Most DS cases are caused by full triplication of chromosome 21, and a small number of cases arise from mosaicism or chromosomal translocations, resulting in multiple medical and physical manifestations. Common characteristics of individuals with DS include skeletal anomalies, craniofacial alterations, hypotonia, increased incidence of congenital heart disease and seizures, abnormalities of the gastrointestinal tract, thyroid dysfunction, and premature aging [1]. Additional clinical features include altered folate metabolism and hormone imbalances [2, 3]. Neurological changes include reduced brain mass, impaired neuronal differentiation, aberrant dendritic spine morphology, and defects in synaptic plasticity [4]. Most middle-aged individuals with DS develop Alzheimer’s disease (see chapter “Alzheimer’s disease”) due to increased expression of the amyloid precursor protein gene located on chromosome 21 [5]. Alterations in reactive oxygen species (ROS) and energy metabolism have long been associated with the development and progression of DS neuropathology [6]. This section focuses on the role of oxidative stress, mitochondrial dysfunction, and hypothyroidism in DS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Roizen NJ, Patterson D (2003) Down’s syndrome. Lancet 361:1281–1289

    Article  PubMed  Google Scholar 

  2. Shaw CK, Thapalial A, Nanda S, Shaw P (2006) Thyroid dysfunction in Down syndrome. Kathmandu Univ Med J (KUMJ) 4:182–186

    CAS  Google Scholar 

  3. Patterson D (2009) Molecular genetic analysis of Down syndrome. Hum Genet 126:195–214

    Article  CAS  PubMed  Google Scholar 

  4. Lott IT (2012) Neurological phenotypes for Down syndrome across the life span. Prog Brain Res 197:101–121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mann DM, Esiri MM (1989) The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down’s syndrome. J Neurol Sci 89:169–179

    Article  CAS  PubMed  Google Scholar 

  6. Coskun PE, Busciglio J (2012) Oxidative stress and mitochondrial dysfunction in Down’s syndrome: relevance to aging and dementia. Curr Gerontol Geriatr Res 2012:383170

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lott IT, Head E, Doran E, Busciglio J (2006) Beta-amyloid, oxidative stress and down syndrome. Curr Alzheimer Res 3:521–528

    Article  CAS  PubMed  Google Scholar 

  8. Brooksbank BW, Martinez M, Balazs R (1985) Altered composition of polyunsaturated fatty acyl groups in phosphoglycerides of Down’s syndrome fetal brain. J Neurochem 44:869–874

    Article  CAS  PubMed  Google Scholar 

  9. Slonim DK, Koide K, Johnson KL, Tantravahi U, Cowan JM, Jarrah Z, Bianchi DW (2009) Functional genomic analysis of amniotic fluid cell-free mRNA suggests that oxidative stress is significant in Down syndrome fetuses. Proc Natl Acad Sci U S A 106:9425–9429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Busciglio J, Yankner BA (1995) Apoptosis and increased generation of reactive oxygen species in Down’s syndrome neurons in vitro. Nature 378:776–779

    Article  CAS  PubMed  Google Scholar 

  11. Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H, Yankner BA (2002) Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down’s syndrome. Neuron 33:677–688

    Article  CAS  PubMed  Google Scholar 

  12. Wang C, Youle RJ (2009) The role of mitochondria in apoptosis*. Annu Rev Genet 43:95–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Helguera P, Seiglie J, Rodriguez J, Hanna M, Helguera G, Busciglio J (2013) Adaptive downregulation of mitochondrial function in down syndrome. Cell Metab 171:132–140

    Article  Google Scholar 

  14. Pfeiffer M, Kayzer EB, Yang X, Abramson E, Kenaston MA, Lago CU, Lo HH, Sedensky MM, Lunceford A, Clarke CF, Wu SJ, McLeod C, Finkel T, Morgan PG, Mills EM (2011) Caenorhabditis elegans UCP4 protein controls complex II-mediated oxidative phosphorylation through succinate transport. J Biol Chem 286:37712–37720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Garcia O, Torres M, Helguera P, Coskun P, Busciglio J (2010) A role for thrombospondin-1 deficits in astrocyte-mediated spine and synaptic pathology in Down’s syndrome. PLoS One 5:e14200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Iwamoto T, Yamada A, Yuasa K, Fukumoto E, Nakamura T, Fujiwara T, Fukumoto S (2009) Influences of interferon-gamma on cell proliferation and interleukin-6 production in Down syndrome derived fibroblasts. Arch Oral Biol 54:963–969

    Article  CAS  PubMed  Google Scholar 

  17. Nickoloff BJ, Riser BL, Mitra RS, Dixit VM, Varani J (1988) Inhibitory effect of gamma interferon on cultured human keratinocyte thrombospondin production, distribution, and biologic activities. J Invest Dermatol 91:213–218

    Article  CAS  PubMed  Google Scholar 

  18. Maheshwari RK, Banerjee DK, Waechter CJ, Olden K, Friedman RM (1980) Interferon treatment inhibits glycosylation of a viral protein. Nature 287:454–456

    Article  CAS  PubMed  Google Scholar 

  19. Kanavin OJ, Aaseth J, Birketvedt GS (2000) Thyroid hypofunction in Down’s syndrome: is it related to oxidative stress? Biol Trace Elem Res 78:35–42

    Article  CAS  PubMed  Google Scholar 

  20. Kennedy RL, Jones TH, Cuckle HS (1992) Down’s syndrome and the thyroid. Clin Endocrinol (Oxf) 37:471–476

    Article  CAS  Google Scholar 

  21. Chen MH, Chen SJ, Su LY, Yang W (2007) Thyroid dysfunction in patients with Down syndrome. Acta Paediatr Taiwan 48:191–195

    PubMed  Google Scholar 

  22. Carroll KN, Arbogast PG, Dudley JA, Cooper WO (2008) Increase in incidence of medically treated thyroid disease in children with Down syndrome after rerelease of American Academy of Pediatrics Health Supervision guidelines. Pediatrics 122:e493–e498

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lott IT (2012) Antioxidants in Down syndrome. Biochim Biophys Acta 1822:657–663

    Article  CAS  PubMed  Google Scholar 

  24. Shichiri M, Yoshida Y, Ishida N, Hagihara Y, Iwahashi H, Tamai H, Niki E (2011) alpha-Tocopherol suppresses lipid peroxidation and behavioral and cognitive impairments in the Ts65Dn mouse model of Down syndrome. Free Radic Biol Med 50:1801–1811

    Article  CAS  PubMed  Google Scholar 

  25. Tiano L, Busciglio J (2012) Mitochondrial dysfunction and Down’s syndrome: is there a role for coenzyme Q(10)? Biofactors 37:386–392

    Article  Google Scholar 

  26. Tiano L, Padella L, Santoro L, Carnevali P, Principi F, Brugè F, Gabrielli O, Littarru GP (2012) Prolonged coenzyme Q10 treatment in Down syndrome patients: effect on DNA oxidation. Neurobiol Aging 33(626):e1–e8

    Google Scholar 

  27. Miles MV, Patterson BJ, Chalfonte-Evans ML, Horn PS, Hickey FJ, Schapiro MB, Steele PE, Tang PH, Hotze SL (2007) Coenzyme Q10 (ubiquinol-10) supplementation improves oxidative imbalance in children with trisomy 21. Pediatr Neurol 37:398–403

    Article  PubMed  Google Scholar 

  28. de la Torre R, Dierssen M (2012) Therapeutic approaches in the improvement of cognitive performance in Down syndrome: past, present, and future. Prog Brain Res 197:1–14

    Article  PubMed  Google Scholar 

  29. Fowler PB, McIvor J, Sykes L, Macrae KD (1996) The effect of long-term thyroxine on bone mineral density and serum cholesterol. J R Coll Physicians Lond 30:527–532

    CAS  PubMed  Google Scholar 

  30. Thiel R, Fowkes SD (2007) Down syndrome and thyroid dysfunction: should nutritional support be the first-line treatment? Med Hypotheses 69:809–815

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders (iMIND), Center for the Neurobiology of learning and Memory (CNLM), University of California – Irvine, 3216 Biological Sciences III, Irvine, CA, 92697-4545, USA

    Maria D. Torres & Jorge Busciglio

Authors
  1. Maria D. Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jorge Busciglio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jorge Busciglio .

Editor information

Editors and Affiliations

  1. Institute of Metabolic Physiology, German Diabetes Center, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

    Eckhard Lammert

  2. CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany

    Martin Zeeb

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Wien

About this chapter

Cite this chapter

Torres, M.D., Busciglio, J. (2014). Down Syndrome. In: Lammert, E., Zeeb, M. (eds) Metabolism of Human Diseases. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0715-7_10

Download citation

Publish with us

Policies and ethics

Search

Navigation