Prenatal diagnosis of hereditary red cell membrane defect

The red cells of a severely anaemic 2-year-old child of a white British family showed high haemolytic fragility with poikilocytosis. The cells showed markedly impaired thermal stability. The mother was phenotypically normal, but the father's red cells showed mild elliptocytosis. The spectrin from the latter, extracted at low temperature, was 30% dimeric (cf. 5-10% in normals). Tryptic digests of the spectrin from both father and daughter showed a reduction in the fragment of 80,000 molecular weight, derived from the terminus of the alpha-chain, and the elevation of a fragment of molecular weight 46,000, as well as one of 53,000. These characteristics and the autosomal recessive inheritance lead to a diagnosis of type II hereditary pyropoikilocytosis, so far reported only in two black American families (Lawler et al, 1983). The spectrin from the father was examined with respect to thermal conformational stability, and was found to be normal. The spectrin from the cells of the daughter gave evidence of the presence of oxidative (disulphide) cross-links, as well as of extensive noncovalent aggregation. Blood was obtained from the umbilical cord vein of the 19-week fetus of the pregnant mother: 250 microliters of blood was used for preparation of red cell membranes for SDS-gel electrophoresis and for extraction of spectrin. Analysis of the spectrin by gel electrophoresis in the native state revealed that the proportion of dimer was within the normal range, and the fetus therefore did not possess the hereditary pyropoikilocytosis phenotype. It is suggested that the procedures described could be generally applied to the prenatal identification of phenotypes associated with severe haemolytic anaemias.