Serum ferritin, serum nitric oxide, and cognitive function in pediatric thalassemia major

  • Septiana Nur Qurbani Department of Child Health, Universitas Padjadjaran Medical School/Dr. Hasan Sadikin Hospital, Bandung, West Java
  • Lelani Reniarti Department of Child Health, Universitas Padjadjaran Medical School/Dr. Hasan Sadikin Hospital, Bandung, West Java
  • Alex Chairulfatah Department of Child Health, Universitas Padjadjaran Medical School/Dr. Hasan Sadikin Hospital, Bandung, West Java
Keywords: thalassemia major, ferritin, nitric oxide, cognitive functions, WISC-R, pediatric


Background Hemolysis and repeated blood transfusions in children with thalassemia major cause iron overload in various organs, including the brain, and may lead to neurodegeneration. Hemolysis also causes decreased levels of nitric oxide, which serves as a volume transmitter and slow dynamic modulation, leading to cognitive impairment.

Objective To assess for correlations between serum ferritin as well as nitric oxide levels and cognitive function in children with thalassemia major. 

Methods This analytical study with cross-sectional design on 40 hemosiderotic thalassemia major patients aged 6−14 years, was done at the Thalassemia Clinic in Dr. Hasan Sadikin Hospital, Bandung, West Java, from May to June 2015. Serum ferritin measurements were performed by an electrochemiluminescence immunoassay; serum nitric oxide was assayed by a colorimetric procedure based on Griess reaction; and cognitive function was assessed by the Wechsler Intelligence Scale for Children test. Statistical analysis was done using Spearman’s Rank correlation, with a significance value of 0.05.

Results Abnormal values in verbal, performance, and full scale IQ were found in 35%, 57.5% and 57.5%, respectively. Serum nitric oxide level was significantly correlated with performance IQ (P=0.022), but not with verbal IQ (P=0.359) or full scale IQ (P=0.164). There were also no significant correlations between serum ferritin level and full scale, verbal, or performance IQ (P=0.377, 0.460, and 0.822, respectively).

Conclusion Lower serum nitric oxide level is significantly correlated to lower cognitive function, specifically in the performance IQ category. However, serum ferritin level has no clear correlation with cognitive function.


1. Galanello R, Origa R. Beta thalassemia. Orphanet J Rare Dis. 2010;5:1−15.
2. Rund D, Rachmilewitz E. β-thalassemia. N Engl J Med. 2005;353:1135−44.
3. Malik S. Complications in transfusion-dependent patients of beta thalassemia major: a review. Pak J Med Sci. 2009;25:678−82.
4. Prabhu R, Prabhu V. Iron overload in Beta Thalassemia- A Review. J Biosci Tech. 2009;1:20−31.
5. Sadrzadeh SMH, Saffari Y. Iron and brain disorders. Am J Clin Pathol. 2004;121:S64−70.
6. Mayer B, Hemmens B. Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem Sci 1997;22:477−81.
7. Mazzone L, Battaglia L, Andreozzi F, Romeo MA, Mazzone D. Emotional impact in β-thalassemia major children following cognitive-behavioural family therapy and quality of life of caregiving mothers. Clin Practice and Epidemiol Mental Health. 2009;5:5:1−6.
8. Steinrt J, Kopp-Scheinpflug C, Baker C, Challiss RA, Mistry R, Haustein MD, et al. Nitric oxide is a volume transmitter regulating postsynaptic excitability at a glutamateric synapse. Neuron. 2008;26:642−56.
9. Zafeiriou D, Economu M, Athanasiou-Metaxa M. Neurological complications in beta-thalassemia. Brain Dev. 2006;28:477−81.
10. Duman O, Arayici S, Fettahoglu C. Neurocognitive function in patients with b-thalassemia major. Pediatr Int. 2011;53:519−23.
11. Wechsler D. Wechsler Intelligence Scale for Children. third ed. San antonio: TX: Psychological Corporation; 1991.
12. Electrochemiluminescence immunoassay (ECLIA) for the in vitro quantitative determination of ferritin in human serum or plasma. Available from:
13. Chemicals C. Nitrate/Nitrite Colorimetric Assay Kit. USA; Available from:
14. Economou M, Zafeiriou D, Kontopoulos E, Gompakis N, Koussi A. Perifanis V. Neurophysiologic and intellectual evaluation of beta-thalassemia patients. Brain Dev. 2006;28:14−8.
15. Raafat N, Safy UE, Khater N, Hassan T, Hassan B, Siam A, et al. Assessment of Cognitive Function in Children With Beta-Thalassemia Major: A Cross Sectional Study. J Child Neurol. 2014:1−6.
16. Bayraktar NN, Erkurt M, Aydogdu I, Baflaran Y. The levels of nitric oxide in beta-thalassemia minor. Turk J Hematol. 2008;25:187−89.
17. Ai Y, Zhao SR, Zhou G, Ma X, Liu J. Hemoglobin status associated with performance IQ but not verbal IQ in Chinese preschool children. Pediatr International. 2012;54:669−75.
18. Evan-Gelder W, Huijskes-Heins M, Cleton-Soeteman M. Iron uptake in blood-brain barrier endothelial cells cultured in iron depleted and iron-enriched media. J Neuroche. 1998;998:1134−40.
19. Monastero R, monastero G, Ciaccio C. Cognitive deficits in beta-thalassemia major. Acta Neurol Scand. 2000;102:162−68.
20. Fosburg M, Nathan D. Treatment of cooley's anemia. Blood. 1990;76:435−44.
21. Retnani HI. Korelasi antara kadar feritin serum dan fungsi kognitif pada anak dengan thalassemia mayor [tesis]. Yogyakarta: Universitas Gajah Mada; 2013.
How to Cite
Qurbani S, Reniarti L, Chairulfatah A. Serum ferritin, serum nitric oxide, and cognitive function in pediatric thalassemia major. PI [Internet]. 22Jun.2017 [cited 14Jul.2024];57(3):149-3. Available from:
Received 2016-09-15
Accepted 2017-06-12
Published 2017-06-22