G. R. Serjeant

OUTBREAK OF APLASTIC CRISES IN SICKLE CELL ANAEMIA ASSOCIATED WITH PARVOVIRUS-LIKE AGENT

Since 1952, 112 children with sickle cell anaemia (SCA) in Jamaica have had an aplastic crisis. Outbreaks occurred in 1956, 1960, 1065-67, 1971-73, and 1979-80. Most cases occurred in children under 10 years of age, and an aplastic crisis in a patient over the age of 15 years is rare. There were 38 cases in 1979-80 and stored serum specimens from 28 of these were available for virus studies. Evidence for infection with a parvovirus-like agent was found in 24 of these 28 cases. Viral antigen was detected in 2 patients, both of whom demonstrated seroconversion. Seroconversion during 1980 was detected in a further 7, increasing amounts of antibody during the convalescent period were found in 5, antibody was found in 2 of 4 patients from whom only an acute phase specimen was available and the remaining 10 were antibody positive in the only convalescent phase sample available for testing. Antibody was found in 4 of 94 controls with the SS genotype (in retrospect 2 of these may have had an aplastic crisis) and in 17% of 48 controls with a normal haemoglobin (AA) genotype. The results accord with the possibility that the parvovirus-like agent is the principal cause of aplastic crisis in SCA.

STILBOESTROL AND STUTTERING PRIAPISM IN HOMOZYGOUS SICKLE-CELL DISEASE

A double-blind, placebo-controlled crossover study was conducted in 11 patients with stuttering attacks of priapism and homozygous sickle-cell (SS) disease. Stilboestrol 5 mg daily was better than the placebo in preventing attacks.

Two different forms of homozygous sickle cell disease occur in Saudi Arabia.

Haematological, clinical and some molecular genetic features of homozygous sickle cell (SS) disease in Saudi Arabia have been compared in 33 patients from the Eastern Province (Eastern) and 30 from the South Western Province (Western). Eastern patients all had the Asian beta globin haplotype whereas Western patients were more variable but predominantly of the Benin haplotype. Eastern patients had more deletional alpha thalassaemia, higher total haemoglobin and fetal haemoglobin levels, and lower HbA2, mean cell volume, reticulocytes, and platelet counts. Clinically, Eastern patients had a greater persistence of splenomegaly, a more normal body build and greater subscapular skin fold thickness, and Western patients had more dactylitis and acute chest syndrome. Painful crises and avascular necrosis of the femoral head were common and occurred equally in both groups. The disease in the Eastern province has many mild features consistent with the higher HbF levels and more frequent alpha thalassaemia but bone pathology (painful crises, avascular necrosis of the femoral head, osteomyelitis) remains common. The disease in the West is more severe consistent with the Benin haplotype suggesting an African origin.

ORAL ZINC SULPHATE IN SICKLE-CELL ULCERS

Abstract In a controlled trial on the effect of oral zinc sulphate in the healing of sickle-cell leg ulcers, the healing-rate in the treatment group was three times faster than in the placebo group.

ROLE OF SPLENECTOMY IN HOMOZYGOUS SICKLE CELL DISEASE IN CHILDHOOD

60 Jamaican children with homozygous sickle cell (SS) disease underwent splenectomy, 14 for prophylaxis against recurrent acute splenic sequestration and 46 for treatment of sustained hypersplenism. Age at operation varied from 9 months to 16 years. Patients were followed up for 1 month to 27 years (median 6 years), with a total of 369 years of patient-observation. None of the 3 patients who died, at ages 2 1/2, 6 1/2, and 21 years, had received prophylaxis against infection. Overwhelming sepsis was possible but not confirmed in the first two deaths which occurred 11 months and 2 1/2 years after operation; the third died from chronic renal failure 11 years after splenectomy. After operation, there were no confirmed cases of pneumococcal septicaemia or meningitis, and the commonest clinical event was the acute chest syndrome.

Comparison of homozygous sickle cell disease in Northern Greece and Jamaica

The clinical and haematological features of homozygous sickle cell (SS) disease were compared in 30 Greek and 310 Jamacian patients. Deletional alpha-thalassaemia, which modifies SS disease, is rare among Greek patients, so only Jamacian patients with four alpha-globin genes were included in the control group. Greek patients had higher total haemoglobin concentration and red cell counts, and lower mean cell haemoglobin concentration (MCHC) and reticulocyte counts. They also had a more normal body build and more adults had persistent splenomegaly. Fewer had a history of leg ulceration or priapism but more reported acute chest syndrome. The comparatively mild disease in Greek patients is consistent with less haemolysis and sickling and therefore less bone marrow expansion. In the absence of amelioriating factors such as high HbF concentration or alpha-thalassaemia, these findings may be explained by the low MCHC.

Pneumonia in young children with homozygous sickle cell disease: risk and clinical features

The incidence and clinical features of pneumonia have been examined in children with homozygous sickle cell (SS) disease and in age/sex matched control children with a normal haemoglobin (AA) genotype followed in a cohort study of sickle cell disease from birth.Survival curve analysis indicated a similar incidence of pneumonia in the two genotypes up to the ages of 8 months after which pneumonia became significantly more prevalent in SS disease, the relative risk exceeding a factor of four by 4 years of age. Children with SS disease were also more prone to multiple episodes. Comparison of clinical features in the two genotypes yielded no difference in sex or seasonal involvement, or in the results of bacteriological and radiological investigations. Children with SS disease and pneumonia had an increased frequency and increased duration of hospital admission, and mortality was confined to this group.It is concluded that children with SS disease have an increased prevalence of single and multiple attacks of pneumonia and that these events run a more serous clinical course than in control children.

Detection of alpha thalassaemia in Negro infants.

Summary. A prospective study of 2291 Negro infants in Jamaica showed that approximately 7% of them had detectable levels of Hb Barts (γ4) in the neonatal period. The red cell indices, globin chain biosynthesis And restriction endonuclease mapping of DNA from these infants were used to determine the significance of Hb Barts at birth. The results indicate that the genotypes αα/αα, —α/αα and —α/—α are associated with 0%, 0.1–2%, and greater than 2% Hb Barts respectively. Although trace amounts of Hb Barts may be associated with the genotype —α/αα this is not always the case and therefore haemoglobin analysis in the neonatal period cannot be used to diagnose this genotype with any certainty.

NEGRO α-THALASSÆMIA IS CAUSED BY DELETION OF A SINGLE α-GLOBIN GENE

Abstract Studies in two Jamaican Negro families, including haematological and haemoglobin analysis, haemoglobin synthesis, and globin messenger-RNA assay, have defined two α-thalassaemia phenotypes which resemble the severe (α-thalassaemia 1) and mild (α-thalassaemia 2) forms of the disorder described in Orientals. Genetic analysis suggests that subjects with the α-thalassaemia-1 phenotype are homozygous for the α-thalassaemia-2 determinant. Restriction-endonuclease mapping shows that α-thalassaemia-2 results from the deletion of one of the linked pair of α-chain genes. Hence the genotypes of the α-thal-assaemia heterozygotes and homozygotes in these families are -α/αα and -α/-α respectively. If these are the usual α-thalassaemia genotypes in Negroes, these findings explain the difference in clinical expression of the disorder between Orientals and Negroes—in particular, the absence of haemoglobin Barts hydrops and the rarity of haemoglobin-H disease in Negroes.

Sickle cell‐hereditary persistence of fetal haemoglobin and its differentiation from other sickle cell syndromes

Summary. Some haematological indices were compared in 13 subjects with sickle cell‐hereditary persistence of fetal haemoglobin (S‐HPFH) and in 10 patients with homozygous sickle cell (SS) disease and four patients with sickle cell‐betaγ thalassaemia, all with fetal haemoglobin (HbF) levels of 20% or above. Sickle cell‐betaγ thalassaemia could be differentiated by a high HbA2 level. S‐HPFH could be distinguished from SS disease with a high HbF level by red cell count, HbF level, reticulocyte count, total haemoglobin and total bilirubin level in decreasing power of discrimination.