Defective granulocyte regulation in the Chediak-Higashi syndrome.

Abstract

The serum muramidase activities of four granulocytopenic patients with the Chediak—Higashi syndrome were always strikingly elevated, indicating a markedly increased rate of granulocyte turnover. Two of the patients, both with histologic and clinical evidence of the accelerated (infiltrative) phase of the syndrome, had intermittent hypersplenism manifest by splenomegaly, thrombocytopenia and hemolytic anemia with splenic sequestration. The administration of prednisone to these two patients corrected manifest hypersplenism but only partly corrected the granulocytopenia and elevation of serum muramidase activity. The other two patients were shown to have normal peripheral granulocyte survival, with no evidence of hypersplenism. None of the patients responded to the administration of etiocholanolone with the expected granulocytosis. All four exhibited marked cytoplasmic abnormalities in bone-marrow granulocyte precursors, different from those seen in peripheral granulocytes. These findings are consistent with intramedullary granulocyte destruction.