Gray Platelet Syndrome (GPS) is an autosomal recessive bleeding disorder with large platelets that lack α-granules. We found that mutations of NBEAL2 (neurobeachin-like 2), encoding a BEACH/ARM/WD40 domain protein, cause GPS. We demonstrated that human megakaryocytes and platelets express a unique combination of NBEAL2 transcripts. Proteomic analysis of sucrose-gradient subcellular fractions of platelets indicated that NBEAL2 localizes to the dense tubular system (endoplasmic reticulum) in platelets.

Gray platelet syndrome (GPS) is an in-

Objective.Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder associated with ADA2 mutations. We aimed to investigate the characteristics and ADA2 enzyme activities of patients with DADA2 compared to non-DADA2 patients.Methods.This is a descriptive study of 24 patients with DADA2 who were admitted to the Adult and Pediatric Rheumatology, Pediatric Haematology, and Pediatric Immunology Departments of Hacettepe University. All ADA2 exons were screened by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method.Results.Twenty-four patients with DADA2 were included: 14 with polyarteritis nodosa (PAN)-like phenotype (Group 1); 9 with Diamond-Blackfan anemia (DBA)-like features, and 1 with immunodeficiency (Group 2). Fourteen PAN-like DADA2 patients did not have the typical thrombocytosis seen in classic PAN. Inflammatory attacks were evident only in Group 1 patients. Serum ADA2 activity was low in all patients with DADA2 except one, who was tested after hematopoietic stem cell transplantation. There was no significant difference in ADA2 activities between PAN-like and DBA-like patients. In DADA2 patients with one ADA2 mutation, serum ADA2 activities were as low as those of patients with homozygote DADA2. ADA2 activities were normal in non-DADA2 patients. ADA2 mutations were affecting the dimerization domain in Group 1 patients and the catalytic domain in Group 2 patients.Conclusion.We suggest assessing ADA2 activity along with genetic analysis because there are patients with one ADA2 mutation and absent enzyme activity. Our data suggest a possible genotype–phenotype correlation in which dimerization domain mutations are associated with PAN-like phenotype, and catalytic domain mutations are associated with hematological manifestations.

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Red cell distribution width (RDW) was studied in adults carrying d-b thalassemia traits (db-TT) who were 20±40 years of age (n = 29), b thalassemia traits (b-TT) with an age range of 18±60 years (n = 49), iron de®ciency anemia (IDA) in individuals aged 1±18 years (n = 27), and in controls with an age range of 20±40 years (n = 20). Although red blood cell count, MCV, and MCH values showed no statistically signi®cant differences between db-TT and b-TT, the mean RDW value was signi®cantly higher in db-TT (20.14 1.21) compared to b-TT (14.88 1.77) (P < 0.001). No difference was observed between the means of RDW in db-TT and IDA (18.00 1.94) (P > 0.05). A signi®cant rise in RDW in IDA 5±7 days after initiation of iron therapy (P = 0.00) which was continued to rise up to the 4 th week of therapy was suggested as an important tool in differentiation of IDA from db-TT. These observations could be kept in mind in the differential diagnosis of db-TT from b-TT and IDA by determining the red blood cell count, red cell indices, and RDW only. Am.