Haptoglobin gene polymorphisms in sickle cell disease patients with different beta s-globin gene haplotypes

To investigate the prevalence of haptoglobin [Hp] gene alleles in Kuwaiti sickle cell disease [SCD] patients, who generally have a mild phenotype, and compare the pattern to Nigerian SCD patients whose SCD phenotype is more severe. Hp genotyping was carried out in a group of 82 and 54 SCD patients from Kuwait and Nigeria, respectively, and appropriate Hb AA controls. The Hp genotyping was done using a PCR technique followed by agarose gel electrophoresis. The frequency of the Hp-2 allele was 73.8% among Kuwaiti SCD patients, while the Hp-1 allele predominated among Nigerian patients [60.7%]. However, the differences were not significant [p > 0.05] when the allele distributions were compared between Kuwaiti SCD and their AA counterparts or between Nigerian SCD and their AA controls. There was no association of Hp-2 allele with frequent vaso-occlusive crisis among the Kuwaiti SCD patients. The distribution of Hp alleles appears to follow ethnic and geographical trends. Their role in the pathophysiology of pain crisis is not clear

Chromosome 22q11.2 deletion presenting with immune-mediated cytopenias, macrothrombocytopenia and platelet dysfunction

To repor t a case of chromosome 22q11. 2 deletion presenting with large platelets, platelet dysfunction, immune-mediated thrombocytopenia and neutropenia, in addition to other features of the disease. Case Presentation and Intervention: The patient presented in the neonatal period with tetralogy of Fallot, subtle dysmorphic features and thrombocytopenia. Fluorescent in situ hybridization analysis confirmed the diagnosis of chromosome 22q11.2 deletion. Further investigations showed immune thrombocyto-penia and neutropenia in addition to reduced expression of platelet GPIb and abnormal platelet aggregation studies. CD4:CD8 ratio was reversed. His cardiac abnormality was successfully corrected surgically. He had mild recurrent bacterial infections. Recurrent epistaxis was becoming increas-ingly more severe, and he had cognitive developmental and speech delay. His serum calcium, phosphorus and parathor-mone have remained normal. Immune throm-bocytopenia can coexist with macrothrombocytopenia and platelet dysfunction in chromosome 22q11.2 deletion and may present with significant bleeding episodes

Serum immunoglobulins and igg subclasses in ss patients with Saudi Arabia/haplotype

This study investigates serum immunoglobulin fractions [IgG, IgA and IgM] and IgG subclasses [IgGScs; IgG1-4] in SS patients with the Saudi Arabia/India [SAI] haplotype. The influence of gender, Hb F levels, spleen function and coexistent -thal trait were studied. Immunoglobulins and IgGScs were assayed using nephelometry. s-globin gene cluster haplotyping and -globin genotyping were done using a combination of PCR and allele-specific oligonucleotide hybridization techniques. Twenty-nine steady-state [i.e. not acutely ill] SS patients [23 SAI homozygotes and 6 SAI/Benin compound heterozygotes] and 34 healthy age- and sex-matched Hb AA and AS controls were studied. Mean serum IgG and IgA values were significantly higher in the patient group, while there were no significant differences in the mean IgGScs. The patient group was further subdivided depending on whether the spleen was normally visualized [group 1], partially visualized [group 2] or not visualized [group 3] on 99mTc-labeled tin colloid scintigraphy. There was a significant sequential increase in mean IgG values from group 1 to group 3 but the reverse was true for IgM, while IgA showed no consistent trend. The mean levels of IgG1 and IgG3 were significantly higher in group 3 [p < 0.01]. Hb F level did not influence immunoglobulins or IgGScs, but SS patients with coexistent -thal trait tended to have lower IgG and IgG1 levels. Conclusions: Increased serum IgG is associated with poor splenic function and recurrent infections among SAI patients, while increased IgM is seen mainly in those with relatively normal splenic function

Genetic epidemiology of sickle cell anemia and B-thalassemia in Kuwait

Mutant beta[s] and alpha-beta- thalassemia alleles are found in polymorphic frequencies in the Arabian peninsula. The precise prevalence figures for Kuwait have, however, not been determined. Using PCR and allelepecific oligonucleotide hybridization techniques, we have characterized the alleles found among Kuwaiti SS, beta-thal major and beta-thal intermedia patients. alpha-Globin gene status was determined among the SS patients and their AS relatives. We have also attempted to identify the ethnic ancestries of the groups in which particular mutations were found. Most of our SS patients [75.9%] are homozygous for the Saudi Arabian/India haplotype, although a few with various combinations of the Benin and Bantu haplotypes are seen, alpha-thal determinants were found in 40% of the individuals studied; the -3.7 kb deletion [alpha-thal-2 trait] was the most common, accounting for 30.0% while non-deletional traits were found in -10%. Ten different beta-thal mutations have been identified so far among Kuwaitis. IVS-II-I[G - A] was the commonest in those of Saudi origin, the IVS-1 3 end 25 bp pair deletion was found only in those of Iranian descent. Only three mutations [the IVS-II-1 [G - A], IVS-I-1 [T-C] and codon 8 [-AA] were found in patients with thalassemia intermedia]. A knowledge of these mutations provides a basis for early and definitive diagnosis and promotes realistic genetic counseling and early institution of appropriate therapeutic measures in our patients