HIGH ADENOSINE-DEAMINASE LEVEL AMONG HEALTHY PROBANDS OF DIAMOND-BLACKFAN-ANEMIA (DBA) COSEGREGATES WITH THE DBA GENE REGION ON CHROMOSOME 19Q13

Phenotypic characterization of Diamond Blackfan Anemia (DBA) patients and their relatives was performed in 54 families. Complete blood count , fetal hemoglobin level, erythrocyte i antigen expression, and erythr ocyte adenosine deaminase (eADA) activities were quantitated in patien ts and relatives. eADA was elevated in 28 of 34 transfusion-independen t DBA patients, whereas persistence of erythrocyte i antigen was notic ed in only 10 of 20 DBA patients. High eADA activities were also found in 14 of 149 healthy family members, allowing us to identify an isola ted high eADA phenotype in these families. In contrast, increase in er ythrocyte i antigen expression, elevated fetal hemoglobin levels, and macrocytosis were much less frequently noted in nonaffected members of the DBA families studied. Importantly, isolated high eADA phenotype w as found to be significantly associated with genetic markers on chromo some 19 that segregate with the DBA phenotype. Isolated high eADA phen otype thus seems to reflect a silent phenotype of DBA in affected fami lies. These findings suggest that elevated eADA activity in unaffected individuals needs to be taken into account during genetic assessment of DBA families and could be used for accurate assessment of mode of i nheritance. (C) 1998 by The American Society of Hematology.