THE SIGNIFICANCE OF HAEMOGLOBIN H IN PATIENTS WITH MENTAL RETARDATION OR MYELOPROLIFERATIVE DISEASE

There are many well-defined genetic disorders of the structure or synthesis of haemoglobin. Acquired abnormalities of haemoglobin synthesis seem to be much less common however. Persistence or reactivation of fetal haemoglobin synthesis may occur in various forms of leukaemia and aplastic anaemia or during recovery from bone marrow hypoplasia (reviewed by Weatherall et al, 1974, Alter, 1979, and Weatherall & Clegg, 1981). A reduced level of haemoglobin Az has been found in some patients with iron deficiency anaemia (Wasi et al, 19 68) and persistent embryonic haemoglobin production has been described in newborn infants with chromosomal abnormalities (Huehns et aI, 1964). However, apart from these changes, and the various post-translational alterations in the structure of haemoglobin which occur in conditions such as diabetes mellitus and lead poisoning, there appear to be relatively few acquired conditions in which there are consistent alterations in haemoglobin synthesis. Furthermore, analysis of fetal haemoglobin production in the leukaemias and other bone marrow disorders has told us very little about the regulation of globin chain synthesis or about the pathophysiology of the underlying disorders. There are, however, two disorders of haemoglobin synthesis which seem to have more specific clinical associations. These are the recently described congenital form of haemoglobin H disease which is found together with mental retardation, and the acquired form of haemoglobin H disease which occurs in myeloproliferative disorders of the elderly. Because haematologists may come across these conditions in everyday practice, and since their characterization may further our understanding of the clinical disorders with which they are associated, we shall summarize briefly recent information about the haematological features and molecular pathology of these conditions.