Hypoplastic anaemia in infancy and childhood: erythroid hypoplasia.

In 1936, Josephs reported 'a hypoplastic or aplastic type of anaemia confined to a failure of erythropoiesis' in two children. Diamond and Blackfan (1938) gave a more detailed description of the disorder in four children, and emphasized the features of a chronic progressive anaemia beginning early in infancy, with a tendency to moderate depression of the leucocyte and thrombocyte counts, and selective hypoplasia of the red cell precursors in the bone marrow. Several reports of this disease have appeared since (Rinvik, 1940; Kohlbry, 1941; H0yer, 1942; Rubell, 1942; Robson and Sweeney, 1948; Smith, 1949, 1953, 1959; Palmen and Vahlquist, 1950; Cathie, 1950; Lelong, Joseph, Polonowski, Desmonts and Colin, 1951; Anderson, 1952; Donnelly, 1953; Aldridge and Kidd, 1953; Kass and Sundal, 1953; Verger and Leger, 1953; Fisher and Allen, 1953; Arrowsmith, Burris and Segaloff, 1953; Burgert, Kennedy and Pease, 1954; Diamond, 1954; Harper and Geikie, 1955; Calvert and Robson, 1956; Sundal, 1956; Pearson and Cone, 1957; Gasser, 1957), and a total of about 70 cases have been recorded. The reports have conformed to the original descriptions, with the exception that marrow examinations in some instances have revealed normal or increased numbers of normoblasts (Cathie, 1950). Various terms used to designate this haematological disorder include congenital hypoplastic anaemia, chronic hypoplastic anaemia (Josephs-Diamond-Blackfan type), erythrogenesis imperfecta, congenital pure red cell anaemia, chronic erythroblastopenia and pure red cell aplasia. The aetiology is unknown, but is considered by many to rest in a congenital anomaly of the erythron, and the finding of associated congenital anomalies provides some support for this theory. The identification of anthranilic acid in the urine of some children with this disease suggested the presence of an inborn error of tryptophane metabolism; the administration of riboflavin to these patients resulted in a decrease in the excretion of anthranilic acid, but did not alter the haematological status (Altman and Miller, 1953). Smith (1949) reported the history of a child in whom anaemia developed in early infancy; the maternal antibody titre of anti:A was 1:128,000. It appears that isoimmunization may produce extreme and prolonged depression of the red cell precursors in infancy. Erythroid hypoplasia, in more general terms, is of varied aetiology, and may occur at all ages. Acute hypoplasia may result from toxic, infective or allergic factors (Gasser, 1957), and sudden crises may develop in congenital spherocytosis (Owren, 1948), sickle cell anaemia (Chernoff and Josephson, 1951), and acquired haemolytic anaemia (Seip, 1955). Chronic forms of the disease have been attributed to chemical agents and autoimmune processes (Eisemann and Dameshek, 1954; Bonham Carter, Cathie and Gasser, 1954; Bousser, Christol, Dausset, Rampon, Jallut and Mery, 1955), and have been associated with the presence of thymic tumours. The subject of chronic erythroid hypoplasia in adults has been reviewed by Tsai and Levin (1957), but this report has included cases only where erythroid proportions were reduced in marrow examinations. Various forms of refractory anaemia with hypercellular bone marrow patterns have been described more recently by Dacie, Smith, White and Mollin (1959), and Vilter, Jarrold, Will, Mueller, Friedman and Hawkins (1960). In many instances the aetiology is unknown, and occasionally there have been reports, both in adults and children, of a familial incidence of the disease (Burgert et al., 1954; Diamond, 1954; Loeb, Moore and Dubach, 1953; Wallman, 1956). For some time effective therapy of erythroid hypoplasia in infancy and childhood was restricted to the frequent administration of blood transfusions, though spontaneous remissions were known to occur. Three of 12 children cited by Diamond underwent spontaneous remission. From 1953 onwards, reports have been published concerning the successful use of corticotrophin and cortico-