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A case of prenatally diagnosed autosomal dominant congenital hypoplastic anaemia (Blackfan-Diamond syndrome or Aase congenital anaemia) causing hydrops fetalis is presented. Recommendations for the prenatal management of Blackfan-Diamond syndrome (BDS) include prepregnancy counselling for parents with BDS, detailed and serial fetal ultrasonography and echocardiography, cordocentesis if there are signs of anaemia, consideration of in utero transfusions and planned early delivery if the fetus is affected.

Summary. Four patients with Diamond-Blackfan syndrome (congenital hypoplastic anaemia) whose disease was resistant to corticosteroid treatment and who were red blood cell transfusion-dependent, were given marrow grafts from allogeneic human-leucocyte-antigen (HLA)-identical siblings. The patients were conditioned with regimens including cyclophosphamide and busulfan. Three of four patients had sustained and complete marrow engraftment. One patient showed early signs of haematopoietic recovery but died on day 35 of pulmonary toxicity. The three surviving patients are well with normal haematopoiesis and Karnofsky performance scores of 100%, 3·0, 7·4 and 10·6 years after transplantation. Congenital hypoplastic anaemia can be treated successfully by allogeneic marrow grafts.

Neutropenia is a rare complication of Diamond-Blackfan syndrome (congenital hypoplastic anaemia). Three patients are reported: all had neutropenia as well as anaemia, and to investigate the cause of the neutropenia culture of bone marrow for granulocyte-macrophage colony forming cells (GMCFCs) was performed. Two cases had a low incidence of GMCFCs, but the third case had a high incidence. These findings suggest that myeloid precursors can be abnormal in Diamond-Blackfan syndrome and that the mechanism of neutropenia may, like that of anaemia, vary from patient to patient.

SUMMARYThree Arab children with congenital hypoplastic anaemia are reported. The three children presented with pallor in the first 3 months of life. All were given corticosteroids at different times. The first child is on high doses of prednisone and also needs blood transfusion every 6 weeks. The second child is on 5 mg prednisone every other day and is in remission. The third has been in complete remission for the last 5 years and is on no treatment. None of these children has associated congenital or chromosomal abnormalities.

A 7-year-old male child with congenital hypoplastic anaemia (Diamond-Blackfan), having originally responded to corticosteroids, but having subsequently become refractory and erythroblastopenic since 4 years, was treated with a combination of cyclophosphamide (CY; 2.1 g) and antilymphocytic globulin (ALG; 8 g), both by the intravenous route. Erythroblastic repopulation of the bone marrow, albeit dyserythropoietic in character, reticulocytosis and erythrocytic increment took place, but only for a short period. The significance of these findings is discussed in the light of recent progress in the understanding of the disease and of its treatment.

A case of severe congenital anaemia (Hb levels 3--4 g/dl) is presented. The patient, a 21-year-old female, requires, since the age of two, periodical blood transfusions, but is nevertheless able to lead a normal life as a housewife. Although the case has to be considered as a form of congenital hypoplastic disorder of the erythroid tissue, some of the clinical and haematological features are compatible with a congenital dyserythropoietic state. On the basis of clinical findings it is suggested that it may represent a previously undescribed form of anaemia which shares the features of both hypoplastic and dysplastic congenital affections of erythropoiesis.

In the period 1975-1983 22 patients, aged 4-36 months were seen with severe transient normochromic, normocytic anaemia caused by a transient erythroblastopenia. In 20 patients bone marrow aspirations were obtained; they showed erythroblastopenia. In ten cases we observed young lymphoid cells, suggesting a diagnosis of acute lymphoblastic leukaemia. One patient suspected of a leukaemia, was studied in more detail. All patients showed reticulocytopenia. MCV and HbF were within normal range. During recovery reticulocytosis and higher levels of HbF were found. Except for blood transfusion in most patients, therapy (e.g. corticosteroids) was not necessary. Spontaneous recovery is a feature of this kind of erythroblastopenia, contrasting with congenital hypoplastic anaemia.

This report describes a 2-month-old female with the Aase syndrome, bringing to 8 the total number of cases of this disorder. Features include triphalangeal thumbs and congenital hypoplastic anaemia. The occurrence of this disorder in sibs born to unaffected parents and in both sexes makes autosomal recessive inheritance the most likely aetiology.

A 5-month-old boy with congenital hypoplastic anaemia and triphalangeal thumbs, known as the Aase syndrome, is described. In addition he had unilateral cleft lip and palate and abnormal dermatoglyphics. Only ten cases have been reported previously; these are reviewed. This case is the third patient reported to have the Aase syndrome who also has a cleft lip. Bone marrow cultures failed to stimulate production of erythropoietic precursors.

Normochromic anaemia was diagnosed in two brothers in early infancy. At the time of this report they were aged 10 (M.H.) and 12 (T.H.) years. A defect of the atrial septum was found in both patients. They had slight skeletal malformations. Their haemoglobin values have remained constantly at the level of about 100 g/l and the RBC count at about 3.5 x 10(12)/l. At repeated examinations, both the patients and their parents had low or borderline low erythrocyte enolase levels. Erythropoietin levels were normal and so were numerous other laboratory tests, including analysis for abnormal haemoglobins. The condition could represent a mild form of chronic congenital hypoplastic anaemia.

THE clinical entity originally designated as congenital hypoplastic anaemia1 and more recently termed erythrogenesis imperfecta2 is a rare type of anaemia characterized by an erythroid hypoplasia of the bone marrow, by normocytic and normochromic circulating red cells, and by the lack of response to any of the known erythropoietic agents. In the course of some metabolic studies conducted on one such patient whose anaemia was diagnosed shortly after birth and who had been studied for four years by one of the authors (G. M.), a strongly bluishfluorescent substance was noted in the urine. (This patient has been studied through the kindness of Dr. C. P. Katsampes.) This fluorescent material was identified as anthranilic acid by chromatographic methods3, isolation from the patient's urine, and by spectroscopic techniques. The R F of this fluorescent material was 0.90 in butanol : acetic acid : water, 1 : 1 : 5, in agreement with the R F of a known sample of anthranilic acid. The melting point of the material isolated (144–146°) and the absorption spectrum are identical with comparable data reported in the literature for anthranilic acid.

Six patients suffering from congenital hypoplastic anaemia and treated with prednisone are presented. Three of them responded well and showed reticulocytosis followed by increase of haemoglobin. Prednisone in a daily dosage of 15–20 mg. was effective while less seemed ineffective and higher doses did not give a better response. By giving prednisone intermittently marked growth retardation was avoided during observation periods of 4–13 years. The other three patients responded less well. It was not possible in these cases to elicit reticulocytosis regularly, and reticulocytosis was never followed by a corresponding increase of haemoglobin. One of these patients died from pneumonia at the age of 4 months. The other two have been treated for 4 and 5 years, respectively, with prednisone given intermittently, and with blood transfusions. Only moderate or mild growth retardation was observed.

Diamond Blackfan syndrome (DBS) is a severe congenital hypoplastic anaemia which may be accompanied by an up to 5 fold increase in red cell adenosine deaminase (ADA) activity (1,2). In a study of more than 10 patients with DBS we have found that the correlation between this disorder and elevated red cell ADA activity is not complete. However, we have observed that elevated ADA activity may be present in leukocytes and cultured fibroblasts of some DBS patients, suggesting that the abnormality can extend beyond the erythroid cells. The ADA protein in red cells of patients displaying hyperactivity is apparently normal as judged by a variety of experimental procedures. In a few cases a familial clustering of the anomolous ADA activity is evident, supporting previous observations (1) and indicating that the phenomenon may have a genetical basis. From our studies we can be sure that this hyperactivity is not due to allelic variation at the ADA structural locus and is more likely to result from a trans acting regulatory mechanism. 1. Glader, B.E., Backer, K., and Diamond, L.K. (1983) N. Engl. J. Med. 309, 1486-90. 2. Whitehouse, D.B., Hopkinson, D.A., and Evans, D.I.K. (1984) Lancet II, 1398-99.