Polyneuropathy Associated with Severe Iron Overload and Oxidative Stress in β-Thalassemia Patients

  • Mona H. El-Tagui
  • Khaled M. Salama
  • Mohamed H. El-Sabbagh
  • Eman R. Youness
  • Marwa Ragaey
  • Amina Abdel-SalamEmail author
Original Article


To investigate the frequency of peripheral neuropathy in patients with β-thalassemia, and to assess its relation to iron overload and oxidative stress. Sixty β-thalassemia patients with mean age of 19 ± 4.9 years were recruited. Serum ferritin was quantitatively assessed by enzyme-linked immunoassay and biomarkers of oxidative stress were estimated calorimetrically. Electrophysiological studies using NEMUS 2, Galileu Software were carried out. The patients were separated into two groups: those with abnormal nerve conduction studies (NCS) {Group A; N = 38} and those with normal NCS {Group B; N = 22}. Thirty-eight (63.3%) patients had axonal motor neuropathy as evidenced by abnormal NCS (group A), they showed higher mean serum ferritin (p < 0.01), higher mean malondialdehyde (MDA) (p < 0.01), and lower mean nitrous oxide, total antioxidant capacity, paraoxonase-1 (PON1) (p < 0.01) compared to group B. Bivariate analysis of NCS data demonstrated that abnormal NCS were more frequent in splenectomized patients (p = 0.002), and poorly-chelated patients with serum ferritin ≥ 2000 ng/ml (p = 0.001). Significant variables associated with abnormal motor NCS were entered in stepwise regression analysis and only elevated serum ferritin (p = 0.01) was independently associated with abnormal motor NCS (p = 0.02; 95% CI 1.433–51.791). None of the studied patients had sensory neuropathy or myopathy. Peripheral motor neuropathy may occur in β-thalassemia patients at a high frequency, regardless of their age and gender. Severe iron overload may contribute to the pathogenesis of neuropathy. Other factors including chelation therapy, splenectomy, and oxidative stress might have an enhancing effect that couldn’t be proved in this study.


Polyneuropathy Iron overload Oxidative stress-β-Thalassemia 



We are indebted to every patient included in this study and also their parents for their corporation and their trust. We wish them all the best of health and happiness.


This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Statement of Human Rights

The current study have been approved by Cairo University research ethics committee (IRB) and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Ethical Approval

All procedures performed in the current study were in accordance with the ethical standards of our institutional research committee and with the 1964 Helsinki declaration and its later amendments.

Informed Consent

Informed consent was obtained from all individual participants and/or the legal guardians of participants included in the study.


  1. 1.
    Weatherall DJ, Clegg JB (1981) The thalassemia syndromes, 3rd edn. Blackwell, OxfordGoogle Scholar
  2. 2.
    Stamboulis E, Vlachou N, Drossou-Servou M, Tsaftaridis P, Koutsis G, Katsaros N, Loutradi-Anagnostou A (2004) Axonal sensorimotor neuropathy in patients with beta-thalassemia. J Neurol Neurosurg Psychiatry 75:1483–1486CrossRefGoogle Scholar
  3. 3.
    Economou M, Zafeiriou DI, Kontopoulos E, Gompakis N, Koussi A, Perifanis V, Athanassiou-Metaxa M (2006) Neurophysiologic and intellectual evaluation of beta-thalassemia patients. Brain Dev 28:14–18CrossRefGoogle Scholar
  4. 4.
    Zafeiriou DI, Economy M, Athanasiou-Metaxa M (2006) Neurological complications in beta-thalassemia. Brain Dev 28:477–481CrossRefGoogle Scholar
  5. 5.
    Jomova K, Valko M (2011) Importance of iron chelation in free radical-induced oxidative stress and human disease. Curr Pharm Des 17(31):3460–3473CrossRefGoogle Scholar
  6. 6.
    Pu YM, Wang Q, Qian ZM (1999) Effect of iron and lipid peroxidation on the development of cerebellar granule cells in vitro. Neuroscience 89(3):855–861CrossRefGoogle Scholar
  7. 7.
    Zhao S, Zhang L, Xu Z, Chen W (2013) Neurotoxic effects of iron overload under high glucose concentration. Neural Regen Res 8(36):3423–3433PubMedPubMedCentralGoogle Scholar
  8. 8.
    Albers JW, Donofrio PD, McGonagle TK (2016) Nerve conduction manual. e-book; Section 4. Table 1 supplement.Pdf retrieved and downloaded from on Aug 2016
  9. 9.
    Nair V, Turner GA (1984) The thiobarbituric acid test for lipid peroxidation: structure of the adduct with malondialdehyde. Lipids 19:804–805CrossRefGoogle Scholar
  10. 10.
    dos Santos AA, Naime AA, de Oliveira J, Colle D, dos Santos DB, Hort MA, Farina M (2016) Long-term and low-dose malathion exposure causes cognitive impairment in adult mice: evidence of hippocampal mitochondrial dysfunction, astrogliosis and apoptotic events. Arch Toxicol 90(3):647–660CrossRefGoogle Scholar
  11. 11.
    Dawson B, Trapp RG (2001) Statistical methods for multiple variables. Basic and clinical biostatistics, 4th edn. LANGE Basic ScienceGoogle Scholar
  12. 12.
    Logothetis J, Constantoulakis M, Economidou J, Stefanis C, Hakas P, Augoustaki O, Bilek M (1972) Thalassemia major (homozygous beta-thalassaemia). A survy of 138 cases with emphasis on neurologic and muscular aspects. Neurology 22:294–304CrossRefGoogle Scholar
  13. 13.
    Zafeiriou DI, Kousi AA, Tsantali CT, Kontopoulos EE, Augoustidou-Savvopoulou PA, Tsoubaris PD, Athanasiou MA (1998) Neurophysiological evaluation of long-term desferrioxamine therapy in beta-thalassemia patients. Pediatr Neurol 18:420–424CrossRefGoogle Scholar
  14. 14.
    Papanastasiou DA, Papanicolaou D, Magiakou AM, Beratis NG, Tzebelikos E, Papapetropoulos T (1991) Peripheral neuropathy in patients with beta-thalassaemia. J Neurol Neurosurg Psychiatry 54:997–1000CrossRefGoogle Scholar
  15. 15.
    Sawaya RA, Zahed L, Taher A (2006) Peripheral neuropathy in thalassaemia. Ann Saudi Med 26(5):358–363CrossRefGoogle Scholar
  16. 16.
    Levine JE, Cohen A, MacQueen M et al (1997) Sensorimotor neurotoxicity associated with high-dose deferoxamine treatment. J Pediatr Hematol Oncol 19:139–141CrossRefGoogle Scholar
  17. 17.
    Kattamis C, Lazaropoulou C, Delaporta P, Apostolakou F, Kattamis A, Papassotiriou I (2011) Disturbances of biomarkers of iron and oxidant–antioxidant homeostasis in patients with beta-thalassemia intermedia. Pediatr Endocrinol Rev 8(Suppl 2):256–262PubMedGoogle Scholar
  18. 18.
    Zohaib M, Ansari SH, Hashim Z, Shamsi TS, Zarina S (2016) Serum paraoxonase activity and malondialdehyde serum concentrations remain unaffected in response to hydroxyurea therapy in β-thalassemia patients. J Clin Pharma 56(7):869–874CrossRefGoogle Scholar
  19. 19.
    Naithani R, Chandra J, Bhattacharjee J, Verma P, Narayan S (2006) Peroxidative stress and antioxidant enzymes in children with beta-thalassemia major. Pediatr Blood Cancer 46(7):780–785CrossRefGoogle Scholar
  20. 20.
    Friedman J (2011) “Why is the nervous system vulnerable to oxidative stress?” Oxidative stress and free radical damage in neurology. Humana Press, New York, pp 19–27CrossRefGoogle Scholar
  21. 21.
    Kehrer JP (1993) Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol 23:21–48CrossRefGoogle Scholar
  22. 22.
    Romay CH, Gonzalez R, Ledon N, Remirez D, Rimbau V (2003) phycocyanin: a biliprotein with antioxidant, anti-inflammatory and neuroprotective effects. Curr Protein Pept Sci 4(3):207–216CrossRefGoogle Scholar
  23. 23.
    Dajas F, Rivera-Megret F, Blasina F, Arredondo F, Abin-Carriquiry JA, Costa G, Morquio A (2003) Neuroprotection by flavonoids. Braz J Med Biol Res 36(12):1613–1620CrossRefGoogle Scholar
  24. 24.
    Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA (2005) Uric acid and oxidative stress. Curr Pharm Des 11(32):4145–4151CrossRefGoogle Scholar

Copyright information

© Indian Society of Hematology and Blood Transfusion 2018

Authors and Affiliations

  1. 1.Department of PediatricsCairo UniversityCairoEgypt
  2. 2.Department of Pediatrics and NeurophysiologyNational Institute of Neuromotor SystemCairoEgypt
  3. 3.Department of Medical BiochemistryNational Research Centre (NRC)GizaEgypt

Personalised recommendations