Erythrocyte glutathione is a novel biomarker of Diamond-Blackfan anemia.
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.
Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
Taiju
T
Utsugisawa
Medical Toukei Co., Tokyo, Japan.
Toshitaka
T
Uchiyama
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Tsutomu
T
Toki
Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
Hiromi
H
Ogura
Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan.
Takako
T
Aoki
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan.
Isao
I
Hamaguchi
Division of Hematology, National Center for Child Health and Development, Tokyo, Japan.
Akira
A
Ishiguro
Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan.
Akira
A
Ohara
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Seiji
S
Kojima
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Shouichi
S
Ohga
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Etsuro
E
Ito
Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Tokyo, Japan; Division of Genomic Medicine, Department of Advanced Biomedical Engineering and Science, Graduate School of Medicine, Tokyo Women's Medical University, Tokyo, Japan. Electronic address: kanno.hitoshi@twmu.ac.jp.
Hitoshi
H
Kanno
D000243:Adenosine Deaminase; D029503:Anemia, Diamond-Blackfan / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004912:Erythrocytes / Q000737:chemistry*; D005190:Family; D005260:Female; D005978:Glutathione / Q000097:blood*; D006801:Humans; D008297:Male; D009154:Mutation; D012269:Ribosomal Proteins / Q000235:genetics
D015415:Biomarkers; D012269:Ribosomal Proteins; D000243:Adenosine Deaminase; D005978:Glutathione
Adenosine deaminase; Antioxidant; Congenital red cell aplasia; Erythrocyte; Ribosomal insufficiency