Dysgranulopoietic neutropenia and abnormal monocytes in childhood vitamin B12 deficiency

Abstract

Neutropenia and/or leukopenia (associated with elevated serum lysozyme levels) in three children with vitamin B₁₂ deficiency were evaluated using soft agar culture and ultrastructural and cytochemical techniques. In two patients a marked increase in peripheral blood myeloid colony forming cells (CFC) was observed; whereas a marginal increase in CFC was present in the third, less symptomatic, patient. Marrow CFC was normal or slightly increased. Serum colony stimulating activity (CSA) was normal but elaboration of CSA by white blood cells was low. Normal maturation of the progenitors was present in vitro and serum inhibitors of myelopoiesis were absent. Megaloblastic neutrophils and monocytes with nuclear‐cytoplasmic asynchrony were observed ultrastructurally in directly sampled marrow specimens. These cells contained autophagic and/or heterophagic vacuoles and an increase in cytoplasmic granules. Both monocytes and neutrophils also contained enlarged‐disrupted centrioles. Many marrow macrophages contained phagocytic vacuoles, which enclosed disrupted neutrophils and cellular debris. We conclude that although a large number of dysmorphic myeloid cells degenerate in the marrow, sufficient marrow CFC are present and peripheral blood CFC are elevated, suggesting abnormal release and/or maturation failure. All of these abnormalities are corrected by administration of vitamin B₁₂.