Diagnosis of pyruvate kinase deficiency in the presence of an elevated reticulocyte count

Abstract

Three members of one family (mother, now aged 44 years; daughter, now aged 23 years, and son, now aged 19 years) have had chronic haemolytic anaemia since their infancy. All three have had several blood transfusions a year because of haemoglobin (Hb) concentrations as low as 5 g/dl due to intermittent increases in haemolysis. Despite an unclear diagnosis all three had splenectomies: their spleens had been enlarged to about 5-7 cm below the rib margin. After splenectomy their haemoglobin concentration rose to 9-12 g/dl and the previously raised reticulocyte count of 150-250/1000 rose further to 400-700/1000. None of the patients had symptoms other than a slight decrease in exercise tolerance. They were admitted to hospital for further evaluation. Physical examination was unremarkable except for slight jaundice and well healed splenectomy scar. All three patients had normochromic haemolytic anaemia (Hb 10-12 g/dl), bilirubin 2-3 mg/dl, lactate dehydrogenase activity 400-600 U/l). The reticulocyte count was raised to 420-690/1000. In all of them pyruvate kinase (PK) activity was normal or slightly increased if related to Hb concentration. Reticulocytes from healthy persons were isolated by density-gradient centrifugation so that samples could be prepared with different numbers of reticulocytes: PK activity was found to be dependent on the sample's reticulocyte count. In the three patients PK deficiency could, therefore, only be diagnosed by taking into account the raised reticulocyte count. As reticulocytes have a higher PK activity than erythrocytes the reticulocyte count must be taken into account when assessing the significance of a given value of this enzyme's activity.