Balanced globin chain synthesis in hereditary persistence of fetal hemoglobin.

In two black families with the hereditary persistence of fetal hemoglobin (HPFH) gene there are eight A-F heterozygotes and two double heterozygotes for sickle cell trait and HPFH. These patients are clinically asymptomatic and have homogeneous acid elution smears. Measurement of globin chain synthesis in peripheral blood demonstrates balanced production of a alpha and non-alpha (beta plus gamma) chains. In these patients, the balance is achieved by increased gamma globin production and increased activity of the remaining beta globin allele. In two patients, one A-F and the other S-F there is also balanced globin synthesis in the bone marrow. In a double heterozygote for HPFH and beta-thalassemia, anemia (Hb: 11.5 g/100 ml) is associated with a moderate degree of globin chain imbalance. There is a correlation between balanced globin chain synthesis and the absence of anemia in patients with HPFH.

Hemoglobin-Strumica or alpha 2 112(G19) His replaced by Arg beta 2. (With an addendum: hemoglobin-J-Paris-I, alpha 2 12(A10) Ala replaced by Asp beta 2, in the same population).

Hemoglobin-Strumica has been observed in five members of a Macedonian family. Histidyl residue in position 112 of the alpha chain of this variant is replaced by an arginyl residue. Two other variants (hemoglobin-Dakar and hemoglobin-Hopkins-2) in which this histidyl residue has been replaced by a glutaminyl and by an aspartyl residue, respectively, have been described (Rosa et al. (1968) 12 thCongr. Int. Soc. Haematol. New York, abstract, p. 73 and Charache, S. and Osterag, W. (1970) Bloodt 36, 852). The hemoglobin-Strumica heterozygotes have minimal hematological changes although this may not necessarily be associated with the hemoglobinopathy. Subjects heterozygous for hemoglobin-Dakar have a mild hemolytic anemia and hemoglobin-Hopkins-2 heterozygotes exhibit minimal hematological changes.

Hemoglobin Athens-Georgia, or alpha 2 beta 2 40(C6)Arg replaced by Lys, a hemoglobin variant with an increased oxygen affinity.

A new hemoglobin variant, termed hemoglobin Athens-Georgia, has been found in a 23-year-old Caucasian student and three members of her family. The electrophoretic mobility of this variant at pH 9.0 is slightly less than that of hemoglobin-A. Arginyl residue in position 40 of the beta chain, corresponding to position 6 of the C helix, has been replaced by a lysyl residue. This amino acid substitution is at the alpha1-beta2 contact and slightly affects the oxygen binding properties of the hemoglobin molecule. Hemoglobin Athens-Georgia has an increased affinity for oxygen, a normal heme-heme interaction and a normal Bohr effect. Hematological abnormalities are not associated with this variant.

Glucose-6-phosphate dehydrogenase deficiency and diabetes mellitus.

This hospital-based study demonstrates a statistically significant higher prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among the Saudi patients with diabetes mellitus (12.4%) as compared to healthy population controls (2.0%) (p less than 0.008). The nature of this association is difficult to explain. In view of a higher frequency of G6PD deficiency among diabetics, it is suggested that all patients with diabetes be screened for this enzymopathy in order to avoid the use of certain drugs or toxic agents that can produce hemolysis.

Heterogeneity of gamma-globin chain synthesis in Saudi newborns.

Cord blood samples from 655 unselected neonates born to Saudi mothers at King Fahad National Guard Hospital, Riyadh, Saudi Arabia were analysed to determine the levels of gamma-globin chains in Saudis. The percentage of three types of gamma-chains of human fetal hemoglobin (A gamma T, G gamma and A gamma I) was obtained by high-performance liquid chromatographic (HPLC) method. Although the majority of babies (631/655) had normal G gamma values in the range of 58-74%, there were only 69% with normal G gamma/A gamma ratio. The A gamma T chain or HbF Sardinia was present in 28% of the total neonates with a gene frequency of 0.160. The A gamma T values in this group ranged between 11-42%. Eight babies (1.2%) had G gamma levels 45% or less (mean 41 +/- 3%) and in 16 neonates (2.4%), G gamma values were highly elevated (mean 81.4 +/- 2.8%). The frequency of two G gamma-globin genes was 0.0061 and 0.0122, respectively, which is comparable with other ethnic or racial groups. The differences in G gamma to A gamma ratio in some Saudi babies could be due to an abnormal arrangement of gamma-globin genes of beta-globin gene cluster which is now being investigated.

Haematological status of blood-donors with sickle cell trait and alpha thalassaemia in northern Nigeria.

Northern Nigeria is an endemic area for sickle haemoglobin (HbS), and it is common practice in many hospitals to accept blood for transfusion from donors with sickle cell trait (HbAS). In 212 healthy HbAS blood donors, the proportion of HbS was found to range between 24-47%. The HbS levels less than 38% were presumably due to the interaction of sickle-cell gene with the alpha + thalassaemia gene. Low HbS levels and presumed alpha + thalassaemia were associated with significant microcytosis and relatively low Hb A2 and Hb F, but differences were minimal. Carriers of sickle cell trait, with or without alpha + thalassaemia, appear to be acceptable as blood donors. Beta thalassaemia was not detected amongst 710 blood-donors.

Blood dyscrasia in unofficial vendors of petrol and heavy oil and motor mechanics in Nigeria.

The risk of blood dyscrasia has been measured in Nigerians exposed to benzene in petrol through inhalation and ingestion while employed selling petrol syphoned from oil-drums at the roadside. Significant degrees of anaemia, hypochromia, neutropenia and thrombocytopenia were found in male vendors of heavy oil for motor scooters (n = 20), vendors of petrol and heavy oil (n = 52) and vendors of petrol alone (n = 46) compared to adolescent (n = 49) and adult (n = 80) male controls. Motor mechanics (n = 57) working at small repair workshops were also at risk of anaemia through exposure to petroleum products. Petrol pump attendants (n = 38) at modern filling stations did not appear to have any such occupational hazard. The practices of unofficial roadside vendors of petrol and heavy oil, and to a less extent motor mechanics, in the developing world are dangerous to health, being associated with blood dyscrasia and probably with increased incidence of aplastic anaemia and leukaemia. Education of the public and legislation are required to stop these practices.

Lead poisoning among Saudi children.

Ten Saudi children with clinical and laboratory findings related to lead intoxication were seen at the King Fahad National Guard Hospital from 1984 to 1988. A presumptive diagnosis of chronic lead poisoning was made retrospectively on 12 other children with hypochromic and microcytic anemia whose other laboratory data were consistent with lead poisoning. The ages of the children ranged from six months to 13 years. After the first child with lead encephalopathy was diagnosed, a high index of suspicion was maintained, thus enabling us to establish an early diagnosis of lead encephalopathy. The findings of this study suggest that excessive lead exposure may still pose a serious public health hazard in Saudi Arabia today which needs to be addressed.

Haematological aspect of malaria in a population based hospital, Saudi Arabia.

In Saudi Arabia, although the malaria is nearly extinct from urban areas, anophelines breeding however still exists in the coastal and oasis regions of the Kingdom. Imported cases of malaria are also seen as the country continues to employ a large expatriate work force from malarious countries. Data were analysed on 69 malaria patients (35 Saudis; 34 non-Saudis) to assess the haematological and clinical manifestations. Two types of malaria, P. falciparum and P. vivax were mainly present. Anemia was the significant finding in patients with P. falciparum (P = 0.0060). Approximately (32/69) half of the patients had Hb < or = 12 g/dl and among these included 15 cases (22%) with Hb < than 9 g/dl. White blood counts were near normal or mildly decreased despite of high fever. Moderate to severe thrombocytopenia (platelets < or = 160 x 10(9)/L) was seen in 57% of the patients and in 10 cases the counts were appreciably low (< 60 x 10(9)/L). Thrombocytopenia correlated with splenomegaly. The palpable spleen was felt in approximately half of patients with P. falciparum. Findings of this study suggest that in Saudi Arabia we will continue to see malaria cases occasionally, however it is important to become aware of the treatment, as many patients who originated from the third world malarious zones, failed to respond to chloroquine therapy.

Neonatal jaundice in Saudi newborns with G6PD Aures.

Sixty-five of 3261 (2%) Saudi neonates were found to be severely G6PD-deficient during a cord blood screening programme conducted from April to December, 1992. However, at the time of molecular studies, the blood samples were available from only 20 randomly selected children, aged from 1 to 6 years. DNA analyses showed that seven (three boys, four girls) of these 20 (35%) had G6PD Aures (nt 143 T - > C), a variant associated with favism which was recently reported in an Algerian. Twelve carried the G6PD Mediterranean (563 T) mutation, and in one child the mutation remained unidentified. The medical records of these children showed that all who had G6PD Aures, including a premature baby, were jaundiced during the 1st week of life, but only six full-term infants had moderate-to-severe hyperbilirubinaemia. Two of seven babies had seizures and one of these two developed kernicterus, in spite of timely blood transfusion.

Increased incidence of hyperbilirubinaemia in 'unchallenged' glucose-6-phosphate dehydrogenase deficiency in term Saudi newborns.

The incidence of severe hyperbilirubinaemia was significantly higher among the G6PD-deficient Saudi infants born at term than in non-deficient babies (34% vs 9%) (p less than 0.005). No apparent offending factors were detected in either the babies or their mothers. All babies who developed hyperbilirubinaemia did so during the 1st week of life. The highest mean bilirubin level for all jaundiced G6PD-deficient babies was recorded on the 4th postnatal day. Although the incidence of severe hyperbilirubinaemia among our neonates was relatively high, only two of them (7%), a boy and a girl, required exchange transfusions. Five of 29 jaundiced babies with G6PD deficiency were readmitted after discharge because of significant jaundice. One required exchange transfusion. Since G6PD deficiency seems to be a relatively common cause of neonatal jaundice in Saudi newborns, early detection of this enzymopathy by cord blood screening is justified to avoid morbidity and deaths.

Hematological values and their assessment as risk factor in Saudi patients with stroke.

The retrospective analysis of hematological data on 500 consecutive Saudi patients (342;158F) (mean age 63 +/- 17 yrs) with stroke whose composition was: large infarctions 260 (52%); lacunar infarctions 121 (24.2%), intracerebral hemorrhage 107 (21.2%) and subarachnoid hemorrhage 12 (2.4%), showed that RBC (5.2 +/- 1.9 x 10(12)/L), Hb (143 +/- 21 g/l) and Hct (0.43 +/- 0.07 1/1) values were significantly higher (P < 0.001) in patients with large infarctions as compared to other types of strokes. In both male and female groups of patients, the most likely stroke prone age was 61 to 70 years and interestingly the levels of above three parameters increased or dropped after a certain age. The highest values were in the 61-70 yr age group with men being higher than women (P < 0.001). The overall mortality rate was about 20%, but it was higher in the group of patients with large infarction (63/260; 24.3%). Of these 13 were below the age of 60 years and the remaining 50 aged > 60 included 28 patients (20M;8F) who had Hb > 140 g/l suggesting that Hb > 150 g/L or Hct > 0.44 in men and > 140 g/l or Hct > 0.42 in women is probably a risk factor for having cerebral infarctions and increased mortality. Since this study is neither a cohort nor prospective and was not performed in the acute phase, it was difficult to ascertain if relative polycythemia was a primary event for stroke or was secondary to dehydration in which Saudi hot weather may be a contributory factor.

Relationship of haemoglobin F and alpha thalassaemia to severity of sickle-cell anaemia in the Eastern Province of Saudi Arabia.

To define the natural history of sickle cell anaemia a cord blood screening programme was initiated and during the first 3 years a total of 129 newborns with FS phenotype were detected, of whom 83 infants were followed up regularly. Forty-three of them had attained the ages of between 1 and 3 years and the analysis of their data revealed that in 21 of 43 cohort children (14 FS and 7 FS + Barts) who had almost identically raised levels of haemoglobin F, the clinical manifestations of the disease appeared to be influenced by the size of the RBC, with the microcytic group having a relatively milder clinical course as compared with the normocytics. Similar observations were made in about 50% (47/93) of non-cohort older children and adults with sickle-cell anaemia, suggesting that alpha thalassaemia in combination with increased levels of fetal haemoglobin was probably an important predictor of the clinical severity in patients with sickle-cell anaemia in the Eastern Province of Saudi Arabia.

Pneumococcal infections in eastern Saudi Arabia: serotypes and antibiotic sensitivity patterns.

The serotypes and antibiotic sensitivity patterns of Streptococcus pneumoniae infections were studied in 208 patients. Male to female ratio was 3 to 1. The main underlying diseases were cardiopulmonary disease (53%), sickle cell disease (13%), diabetes mellitus (11%) and malignancies (11%). The commonest infections were conjunctivitis, bronchopulmonary infections and otitis media. Serotypes 6 and 19 were the most common, especially in children, constituting 66% of the isolates. All the isolates were sensitive to penicillin, ampicillin and vancomycin, but 65% were resistant to cotrimoxazole. Penicillin, therefore, remains the best antimicrobial agent for treatment. All the serotypes are represented in the polyvalent pneumococcal vaccine available in the country; therefore some benefit can be expected from vaccination especially in the high risk patients.

An individual with Hb-Lepore-Baltimore- delta beta-thalassaemia in a Yugoslavian family.

The clinical, haematological and biochemical findings in a person with delta beta-thalassaemia and Hb-Lepore are described. The patient was a 24-year-old student who suffered from anaemia of intermediate severity with late onset of the clinical manifestations, had minor bone and facial deformities, but had no necessity for regular transfusions. Haemoglobins A and A2 were absent in this individual, and the Hb-Lepore has been identified as Lepore-Baltimore. Heterogeneity of gamma chain of the Hb-F follows the expected pattern. The study provides further evidence that neither beta nor delta chains are synthesized in cis to delta beta-thalassaemia or Hb-Lepore.

Variability of sickle cell disease in the Eastern Province of Saudi Arabia.

The clinical and hematologic features of sickle cell disease in two groups of patients of different ancestral origin, but living in the Eastern Province of Saudi Arabia, are presented. Twenty-eight patients of southwestern origin were matched for gender, age, and diagnosis with an equal number of patients of eastern origin. The disease was diagnosed in all patients at birth, and follow-up study was done on a regular basis. Despite being born and living in the same environment (Eastern Province), patients of southwestern origin had more severe clinical features, consistently lower hemoglobin levels, and higher reticulocyte counts, suggesting more severe hemolysis. We conclude that there are at least two distinct forms of sickle cell disease in the Eastern Province of Saudi Arabia and that the variability of the disease in early childhood is more likely related to genetic than to environmental factors.

Serum immunoglobulin and complement levels in patients with sickle cell anaemia from eastern province of Saudi Arabia.

Serum immunoglobulin (IgG, IgA, IgM) and complement (C3, C4) levels were determined in 61 sickle cell anaemia patients of various age groups and both sexes in their steady state by nephelometry. Serum IgG was found to be consistently elevated in 46% cases of all age groups. Increase in the levels of IgA, IgM and in the complement values (C3, C4) was also observed. Although the mechanism responsible for these variations was unclear, however, this study gave an idea about the general pattern of serum immunoglobulin and complement levels in sickle cell anaemia patients from the Eastern Province of Saudi Arabia.