Abstract
Objective
Fanconi anemia (FA) is a rare inherited genomic instability syndrome and usually associated with endocrine dysfunctions. We aimed to assess the diagnostic standards of chromosomal instability in FA and to correlate the breakage frequency with the severity of endocrinal dysfunctions.
Methods
Twenty seven FA patients were randomly selected from Hematology Unit of Mansoura University Children’s Hospital; their mean age 8.8 yr. Sixteen normal children matched for age and sex were used as controls. Cytogenetic studies included peripheral blood lymphocyte cultures using phytohemagglutinin to obtain chromosomal spreads. Chromosomal breakage was induced by (i) Diepoxybutane 0.1 μg/ml. (ii) Mitomycin C 0.1 μg/ml. (iii) Irradiation of cultures to four radiation doses; 75, 150, 300 and 400 rads (rad1, rad2, rad3 and rad4 respectively). Chromosomal aberrations were scored from the previous 6 cultures besides a culture for spontaneous chromosomal breakage; then mean chromosomal breakage was calculated for the seven cultures. Endocrinal evaluation included quantitative determination of thyroid stimulating hormone (TSH) and tetraiodothyronine (T4), serum growth hormone (GH), insulin like growth factor-1 (IGF-1) and insulin levels.
Results
Chromosomal breakage was found to be significantly higher in patients than control when induced by Diepoxybutane (p = 0.003), Mitomycin (p = 0.001), rad3 (p = 0.043) and rad4 (p = 0.001). Mean chromosomal breakage was significantly negative correlated to head circumference (r = −0.57) and GH level (r = −0.50), with no significant correlation to other hormonal parameters. Mitomycin and rad4 were found more accurate than DEB test for diagnosis of FA in suspected cases.
Conclusion
Correction of the frequently associated hormonal dysfunction (reduced GH and T4) should be considered in the treatment discipline of FA patients to improve their final height.
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Al-Haggar, M., Al-Morsy, Z., Yahia, S. et al. Correlation of thyroid and growth hormones to chromosomal instability in Egyptian Fanconi anemia patients. Indian J Pediatr 75, 679–684 (2008). https://doi.org/10.1007/s12098-008-0128-0
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DOI: https://doi.org/10.1007/s12098-008-0128-0