The clinical effects of excessive a globin genes : two family studies

Abstract

INTRODUCTION: Globin chain imbalance is the central pathogenic abnormality in the thalassaemias, a condition where globin gene expression is reduced. Conversely, the inheritance of excess globin genes too may affect the phenotype. However such examples are rarely found. OBJECTIVES: To describe two families in whom the co-existence of excess a genes was noted together with p - thalassaemia trait. METHODS: During the routine P - globin gene analysis in patients attending the Thalassaemia Unit of the Kurunegala Hospital, two patients were identified to have thalassaemia intermedia phenotype, but with just one (3 - thalassaemia mutation. The clinical details of these patients and their families were studied in detail as was their h'aematological and genetic data. RESULTS: We describe two families in which the propositus had inherited six and eight a - genes respectively together with a single p - thalassaemia mutation. Both patients had the thalassaemia intermedia phenotype. The family members who did not inherit any thalassaemic mutations too had varying, but often marked hypochromic microcytosis. DISCUSSION: We describe the first ever family study of a patient with the combination of 8 a - genes and p - thalassaemia trait. We also describe another family where a member had 6 a - genes together with p thalassaemia trait. This highlights yet another mechanism for the intermedia phenotype in patients with a solitary (3 - globin gene mutation. It also highlights the need for the study of a globin genes in patients with unexplained hypochromic microcytic anaemia.