TY - JOUR
T1 - Erythrocyte glutathione is a novel biomarker of Diamond-Blackfan anemia
AU - Utsugisawa, Taiju
AU - Uchiyama, Toshitaka
AU - Toki, Tsutomu
AU - Ogura, Hiromi
AU - Aoki, Takako
AU - Hamaguchi, Isao
AU - Ishiguro, Akira
AU - Ohara, Akira
AU - Kojima, Seiji
AU - Ohga, Shouichi
AU - Ito, Etsuro
AU - Kanno, Hitoshi
N1 - Funding Information:
This work was supported in part by Health and Labor Sciences Research Grants (Research on Rare and Intractable Diseases) from the Ministry of Health, Labour and Welfare, Japan (Grant number H26-NANCHITOU(NAN)-IPPAN-029 ) and by JSPS KAKENHI Grant number 13245575 .
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/7/1
Y1 - 2016/7/1
N2 - Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia with mutations in ribosomal protein (RP) genes. Elevated activity of erythrocyte adenosine deaminase (eADA) has been utilized as a biomarker of DBA. We examined erythrocyte reduced glutathione (GSH) as well as eADA in 22 patients in 18 DBA families, in whom RP gene mutations had been identified. Simultaneous evaluation of both eADA and GSH demonstrated that all examined DBA patients showed elevated values of either eADA or GSH, whereas presence of both eADA and GSH elevation was able to distinguish DBA patients from 34 normal controls and 14 unaffected members of the DBA families. Furthermore, a support vector machines analysis using both eADA and GSH levels yielded a formula to differentiate DBA from both normal controls and non-DBA family members. To confirm the usefulness of the formula, we analyzed additional 7 patients diagnosed by the clinical criteria. Although eADA showed within normal values in 3 patients, all of these patients were diagnosed as 'DBA' by use of the formula. Because extensive analysis of the RP genes failed to detect no causative mutation in approximately 40% of clinically diagnosed DBA patients, GSH may be useful an additional biomarker for diagnosis of DBA.
AB - Diamond-Blackfan anemia (DBA) is a congenital red cell aplasia with mutations in ribosomal protein (RP) genes. Elevated activity of erythrocyte adenosine deaminase (eADA) has been utilized as a biomarker of DBA. We examined erythrocyte reduced glutathione (GSH) as well as eADA in 22 patients in 18 DBA families, in whom RP gene mutations had been identified. Simultaneous evaluation of both eADA and GSH demonstrated that all examined DBA patients showed elevated values of either eADA or GSH, whereas presence of both eADA and GSH elevation was able to distinguish DBA patients from 34 normal controls and 14 unaffected members of the DBA families. Furthermore, a support vector machines analysis using both eADA and GSH levels yielded a formula to differentiate DBA from both normal controls and non-DBA family members. To confirm the usefulness of the formula, we analyzed additional 7 patients diagnosed by the clinical criteria. Although eADA showed within normal values in 3 patients, all of these patients were diagnosed as 'DBA' by use of the formula. Because extensive analysis of the RP genes failed to detect no causative mutation in approximately 40% of clinically diagnosed DBA patients, GSH may be useful an additional biomarker for diagnosis of DBA.
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U2 - 10.1016/j.bcmd.2016.03.007
DO - 10.1016/j.bcmd.2016.03.007
M3 - Article
C2 - 27282564
AN - SCOPUS:84963595007
SN - 1079-9796
VL - 59
SP - 31
EP - 36
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
ER -