The prevalence of ABO blood group antigens and antibodies in Lagos State, Nigeria.

A total of 1239 normal donors from the Lagos University Teaching Hospital (LUTH) and 111 staff of the National Institute for Medical Research (NIMR) Yaba were screened for ABO antibodies. Of the number from LUTH, 220 (17.8%) were found to be in group A, 282 (22.8%) in group B, 85 (6.9%) in group AB and 652 (52.6%) in group O. The number from NIMR consisted of 20 (18.0%) in group A, 25 (22.5%) in group B 8(7.2%) in group AB and 58 (52.3%) in group O. The mean tile avidity time of sera from 789 (62.66%) potent LUTH donors was less than 35 seconds. Only 97 (6.91%) of this reacted within 10 seconds. On the other hand, only 11(9.9%) of the NIMR sera reacted within 35 seconds and none reacted within 10 seconds. Group O individuals from LUTH and NIMR did not always have anti-A and anti-B components of their sera with equal avidity or potency. It was also observed that high avidity of antibody did not necessarily correspond with high potency. The commonest titre for group B (anti-A) sera was 256 and that for group A (anti-B) was 512. In general, anti-B titres tended to be consistently higher than anti-A. There was a bimodal peak at titres 32 and 256 in group B (anti-A) sera. This repeated itself in the anti-A component of group O sera (i.e., anti-A+B), but here the peaks occurred at 32 and 128.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic leg ulcers in sickle cell disease: experience in Ibadan, Nigeria.

The prevalence of chronic leg ulcers was investigated in 872 adults with sickle cell disease (SCD) (630 HbSS and 242 HbSC) at Ibadan, Nigeria. The incidence was 7.5% in HbSS and 1.7% in HbSC patients. The sex ratio in HbSS was 2:1 in favour of males, and three of the four HbSC were females. Ulcers were sited around the ankles in more than 70% of the patients. The duration of the ulcers varied from less than 1 year to more than 20 years. There was no bias for social class. Response to therapy, including autologous skin graft, was poor.

Prevalence of cholelithiasis in Nigerians with sickle cell disease.

Gall bladder ultrasonography was performed on 157 fasting patients (mainly adults) with sickle cell disease (133 SS and 24 SC) with a view to establishing the prevalence of cholelithiasis in Nigerian 'sicklers'. There were 82 females and 75 males whose ages ranged from 9 to 60 years (mean 34.5). Gallstones were demonstrated in 38 patients, giving an overall prevalence of 24.2% (22.6% in SS and 33.3% in SC). Their ages ranged from 18 to 56 years (mean 37.0) in HbS + C patients and 10-34 (mean 22.0) in SS patients. All the patients except one were asymptomatic. Autopsy confirmed gallstones in two SS patients who died of unrelated problems. The higher prevalence obtained in this study (24.2%) compared with the prevalence (less than 10%) in earlier studies from Africa could be due to the predominantly adult age group screened and the greater sensitivity of cholecystosonography.

Foetal haemoglobin levels in sickle cell anaemia in Nigerians.

Many patients with sickle cell anaemia (SCA) are known to synthesize increased amounts of foetal haemoglobin (Hb F). In some situations, the levels attained are so high that the course of the disease is ameliorated since Hb F does not participate in the polymerization process characteristic of the sickling phenomenon. It has also been reported that the simultaneous inheritance of an alpha-thalassaemia gene reduces the severity of SCA. We have examined the levels of Hb F in relation to the erythrocyte indices and the coinheritance of the deletion type alpha-thalassaemia in SCA patients in Nigeria. The concentration of Hb F in peripheral blood was measured by the alkali denaturation technique of Betke et al. [15], whilst erythrocyte indices were determined on a Coulter S plus II counter. Alpha-thalassaemia was detected by the restriction endonuclease analysis of DNA obtained from peripheral white blood cells (WBC) and nucleated red cells using alpha-globin gene-specific probes. The mean Hb F level in 130 SCA subjects was 5.9 +/- 3.8% (range 0.9-16%). Males had significantly lower levels than females. Hb concentration, haematocrit, and Hb A2 did not differ in subjects with Hb F levels lower than 2% (Group I) when compared with those whose Hb F levels were higher than 8% (Group II). The mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) were lower in Group I. Globin analysis in 30 of these subjects showed that 20 had four, eight had three, and two had two alpha-globin genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Sickle cell anaemia in a 60 year old Nigerian.

The case of a sixty-year-old Nigerian with sickle cell anaemia is presented. His steady state haematocrit is 0.26 L/L. Haemoglobin F. and HbA2 measured 7.00% and 2.9% respectively. Bone pain crisis occurred very infrequently (one or less per year) but jaundice is always present. A right nephrectomy for haematuria was carried out in Dublin, Ireland, in 1954 when he had his first ever blood transfusion. He was hospitalised for the first time in Nigeria on 21/7/83 in anaemic cardiac failure with haematocrit of 0.14 L/L during which he had the second blood transfusion. Chronic leg ulcer, avascular necrosis of the femoral head and cholelithiasis were absent. He had led a fairly active life and recently retired (1986) as a bursar from a secondary school.

Hpa-I polymorphism and the sickle gene in Nigerians.

The Hpa-I restriction fragment length polymorphism linked to the beta globin genes was studied in 181 Nigerian subjects. The beta S gene was found to be linked to the 13 kilobase (kb) Hpa-I fragment in 98.4 percent while 1.6 percent was linked to the Hpa-I 7.6 kb fragment. The majority of beta A genes (94.2%) was found to be linked to either the 7.6 or 7.0 kb fragment whilst the remainder (5.8%) was linked to the 13.0 kb. The beta A 13 kb linkage and the small proportion of the beta S genes linked to the 7.6 kb fragment would lessen the accuracy of the Hpa-I polymorphism in the prenatal diagnosis of sickle cell anaemia in this population.

HpaI polymorphism and the sickle gene in Nigerians.

The HpaI restriction fragment length polymorphism linked to the beta globin gene was studied in 181 Nigerian subjects. The beta s gene was found in the 13 kilobase (kb) HpaI fragment in 98.4 percent and in the remaining 1.6 percent of the cases in the HpaI 7.6 kb fragment. The majority of beta A genes (94.2%) were found in either the 7.6 or the 7.0 kb fragment whilst the remainders (5.8%) were in the 13.0 kb fragment. The rare, but not zero, associations of beta A with the 13 kb linkage and of beta s genes with the 7.6 kb fragment would lessen the accuracy in the prenatal diagnosis of sickle cell anaemia in this population through the use of the HpaI polymorphism.

Chronic lymphocytic leukaemia with raised serum IgM levels.

Eight patients diagnosed as having chronic lymphocytic leukaemia (CLL) from clinical and haematological data were also observed to possess immunological characteristics similar to tropical splenomegaly syndrome (TSS). We suggest that the raised IgM level in these cases may be the effect of chronic exposure to malaria in patients who later developed CLL. Consequently, raised serum IgM, which is a feature of TSS, may also be found in some cases of CLL in Nigeria.

Alpha-thalassaemia in Nigeria: its interaction with sickle-cell disease.

We have determined the molecular basis and frequency of alpha-thalassaemia in Nigeria. The alpha-thalassaemia determinant in this population is caused by only one type of single alpha globin gene deletion (-alpha 3.7). Comparison of the haematological features of those patients who have sickle-cell disease with (-alpha/alpha alpha, -alpha/-alpha) or without (alpha alpha/alpha alpha) alpha-thalassaemia showed similar trends to those reported in Jamaican and U.S. patients with these interactions. However, in contrast to studies in some other African populations we have shown that the frequency of alpha-thalassaemia in Nigeria is the same (0.24) in patients with or without homozygous sickle-cell disease (AA, AS and AC genotypes).

Polycythaemia rubra vera associated with unbalanced expression of the X chromosome and monoclonality of T lymphocytes.

Polycythaemia rubra vera (PRV) was diagnosed in a 69-year-old Nigerian woman whose haemolysate revealed an electrophoretically slow-moving homogeneous band of the enzyme glucose 6-phosphate dehydrogenase (G6PD). Further biochemical characterization identified the enzyme as a new sporadic G6PD variant. Electrophoresis of the haemolysate of 4 children of the proposita identified in a daughter a large quantity of the slow-moving variant enzyme, and a much lower quantity of the normal type enzyme, thus, signifying an extremely unbalanced mosaic phenotype situation. All other family subjects studied, including 2 sons, had the normal enzyme type B, thus confirming the heterozygosity of the proposita at the G6PD locus. Homogenates of platelets, granulocytes and E-rosette-forming lymphocytes of the proposita showed an identical slow-moving band as the haemolysate, thus, suggesting the origin of these cells from a common progenitor cell which may be either the pluripotent stem cell (PSC) or another precursor cell at an earlier level of development than the PSC. While the observation of preferential production of the variant enzyme may be attributed to the presence on the X chromosome of a 'haemopoietic gene', its relevance to the etiology of PRV is unclear.

Aplastic anaemia associated with anti-tuberculosis chemotherapy.

3 cases of aplastic anaemia occurring in association with anti-tuberculosis chemotherapy are reported. The patients had been on anti-tuberculosis chemotherapy for 13, 11 and 14 months, respectively, prior to the diagnosis of aplastic anaemia. Agents used included streptomycin, thiacetazone, isoniazid, p-aminosalicylic acid and dimethylcarbazine. Recovery from aplasia did not occur 6. 1.5 and 0.8 months, respectively, after the discontinuation of the suspect myelotoxic agents and despite the use of myelostimulatory agents. All 3 patients died of haemorrhage secondary to thrombocytopenia. The observations are consistent with a protracted and probably irreversible damage of the bone marrow by anti-tuberculosis agent(s) in susceptible individuals.

Hemoglobin chain recombination and the pattern of composition of hemoglobin S and D in heterozygotes.

The pattern of composition of hemoglobin in different heterozygotes for S and D hemoglobins is quantitatively accounted for by the relative rates of combination of the different chains alpha + beta A greater than alpha + beta D greatern than alpha + beta S greater than alpha + gamma. It is suggested that the recombination step may be one of the rate-limiting steps in hemoglobin assembly.

Haemoglobin DIbadan in a haemoglobin S endemic population.

Haemoglobin DIbadan (beta 87 threonine leads to lysine) was originally found in Ibadan, an area with a high incidence of sickle cell haemoglobin (HbS). Since haemoglobin D and S are indistinguishable by most common conventional methods, the geographical coincidence of the two haemoglobin poses a serious screening problem which was investigated in the propositus who is heterozygous for S and D, his wife who is heterozygous for A and S, and their six children. The combined techniques of haemoglobin solubility, sickling rate, shaking test and routine electrophoresis have yielded an unequivocal diagnosis of the haemoglobin types of the family both for identification and quantitative estimation of the percentage of haemoglobins in the heterozygotes. HbD was found to be slightly less soluble than HbA but otherwise normal blood from S+D individuals was found to contain 57-60% HbD suggesting an increased systhesis of HbD relative to S, whereas A+D heterozygote has 41% HbD suggesting a diminished synthesis of HbD relative to HbA. The physicochemical characteristic of HbD and the haematological data in simple heterozygotes are normal.

Genetically determined deficiency of glucose 6-phosphate dehydrogenase (type-A-) is expressed in the liver.

G6PD activity was determined in liver biopsy specimens from 31 patients (25 men and six women). The G6PD genotype of the patients was determined by carrying out on lysates of their red blood cells quantitative assays of the enzyme and starch-gel electrophoresis. In 21 subjects with normal G6PD activity in red cells, a relatively wide variation of G6PD activity was found in liver extracts. By contrast, in 10 subjects with G6PD deficiency, the activity of the enzyme in liver extracts was always low. The difference between the distribution of liver G6PD activity values of G6PD-normal and G6PD-deficient subjects was statistically significant (p less than 0.01). We conclude that G6PD deficiency of the African type is also expressed in the liver. These findings may have a bearing on hyperibilirubinemia, which cannot be entirely attributed to hemolysis, often encountered in G6PD-deficient patients.

Severe malaria and glucose-6-phosphate-dehydrogenase deficiency: a reappraisal of the malaria/G-6-P.D. hypothesis.

Nigerian children with convulsions and Plasmodium falciparium parasitaemia above 100,000/microliter did not show a decreased frequency of glucose-6-phosphate-dehydrogenase (G.-6-P.D.) deficiency. A re-evaluation of earlier studies has led to the conclusion that clinical evidence of protection against falciparum malaria in G.-6-P.D.-deficient individuals is lacking. Evidence for the possible role of malaria in selecting for G.-6-P.D.-deficient genes consists solely of the geographical association of high frequencies of G.-6-P.D. deficiency with endemic malaria.

Genetic heterogeneity of "normal" human erythrocyte glucose-6-phosphate dehydrogenase: an isoelectrophoretic polymorphism.

Quantitative determination of glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate: NADP+ 1-oxidoreductase, EC 1.1.1.49) activity was carried out in 214 male Nigerian children of 84 mothers with known Gd genotype. The relative intrasibship difference in G6PD activity (normalized to the lowest value within the sibship) was below 0.18 in all cases but one when the children were known to have the same Gd+ allele (identical by descent); whereas it was higher than 0.18 in 18 out of 33 sibships in which children might have had either of the two maternal (electrophoretically identical) Gd+ alleles. G6PD from 10 (8 G6PD B and 2 G6PD A) children belonging to four of the sibships possessing high quantitative variation in G6PD activity was partially purified and extensively characterized. The 8 G6PD type B samples fell unambiguously into two classes on the basis of Km values for glucose 6-phosphate (determined at variuos pH values), and KCl gradient elution from DEAE-Sephadex columns. The two types of G6PD B were resolved from an artificial mixture on a DEAE-Sephacel column. The two G6PD type A samples were also different from each other by the same criteria. We conclude that "normal" G6PD is genetically heterogeneous and that the structural Gd alleles concerned are all polymorphic in the Nigerian population. In this instance, a human enzyme polymorphism, not associated with enzyme deficiency, is revealed by an approach other than electrophoresis.

Low erythrocyte pyridoxal-kinase activity in Blacks: Its possible relation to falciparum malaria.

The red-cell glucose-6-phosphate dehydrogenase (G.-6-P.D.) activity and red-cell pyridoxal-kinase (P.L.K.) activity of 27 Nigerian children with severe Plasmodium falciparum parasitaemia were compared with those of 26 healthy Nigerian children and 6 White adults. The mean P.L.K. activity of the malaria patients was similar to that of the Whites but significantly higher than that of the Nigerian controls. Correction for reduced mean red-cell age in patients was made by comparing the P.L.K.: G.-6-P.D. ratio for those subjects with stable G.-6-P.D. phenotypes. The mean P.L.K.:G.-6-P.D. ratio was the same for malaria patients and adult White but significantly higher than that for the Nigerian controls. These results suggest that the relatively high frequency of low red-cell P.L.K. activity among Blacks may have been selected for by falciparum malaria.