Alder Anomaly Accompanied by a Mutation of the Myeloperoxidase Structural Gene

Abstract

In this paper, a third form of Alder anomaly is described. In addition to the morphological changes which are characteristic of this anomaly, the peroxidase of the neutrophil polymorphonuclear leukocytes (NPNL) is abnormal in its properties. It is resistant to the fixation step in the May-Grünwald Giemsa procedure and is similar, therefore, to the eosinophil peroxidase. In the phenotype observed, 2 genetic changes are probably involved: one is a change in the regulation of NPNL granulation, the other is a mutation in the myeloperoxidase structural gene. In the light of these new findings, 3 forms of the anomaly are now known: (a) the original Alder anomaly, in which the abnormal granulation, particularly in the granulocytes, is not linked with any hereditary disorder; (b) the Alder-Reilly form, in which in addition to the abnormal granulation the leukocytes also contain inclusion bodies, the phenomenon sometimes being associated with mucopolysaccharidosis (gargoylism), and (c) the third form of anomaly described here, where – apart from the abnormal granulation – the myeloperoxidase behaves differently, resembling that of eosinophils in its resistance to methanol fixation.

Abnormalities in leukocyte morphology and number

“…Associations with a mutation of the MPO structural gene 69 and with a myelodysplastic syndrome (MDS) 70 have been reported in the literature. It apparently does not inter fere with the leukocyte function.…”