Chromosomal Aberrations in Two Cases of Inherited Aplastic Anemia with Unusual Clinical Features

SUMMARY

Two brothers had aplastic anemia similar to Fanconi anemia but without associated congenital abnormalities. Both had mild clinical courses and prolonged response to androgen therapy, one had persistent remission for 3 years after therapy. Cultured peripheral lymphocytes of both patients showed a high prevalence of chromosomal breaks characteristic of Fanconi anemia. Electron microscopy did not show a morphologic basis for the chromosomal breaks. One brother had a stable translocation chromosome in bone marrow erythroid and myeloid cells. The other's cultured skin fibroblasts showed an increased susceptibility to "malignant" transformation by SV40 virus, a finding also characteristic of Fanconi anemia.

Skin fibroblasts from the normal mother and a normal sister showed an increased susceptibility to "malignant" transformation, suggesting that this test may provide a means of detecting the heterozygous carrier state. Since the patients studied could not be diagnosed as having Fanconi anemia on clinical grounds alone but did appear to represent a variant of the disease on the basis of chromosomal analysis and viral transformation studies, these tests may prove to be useful in distinguishing Fanconi-type anemia from other familial aplastic anemias and in predicting response to therapy.