Admission records of children with sickle cell anemia (SS), in the two main teaching hospitals in Kuwait, were reviewed for a 1-year period. The haplotypes of 92 β^s chromosomes (from 39 SS, 11 AS, 2 Sβ-thalassemia [Sβ -thal] and 1 SD individuals) were determined using an allele-specific oligonucleotide (ASO) hybridization technique, while the α-globin gene status of 27 SS and 33 AS individuals, i.e. 120 chromosomes, was determined with a combination of polymerase chain reaction and ASO techniques. A vasoocclusive crisis was the most common (60.0%) cause of hospitalization, followed by infections (20%). Hospital admissions were most common during the hottest month of the year (July). Few complications of the disease were seen among patients on follow-up; however, splenomegaly was present in 24.0%, hepatomegaly in 15.2%, gallstones in 15.2% and aseptic necrosis of the femoral head in 6.1%. Haplotype 31 (Saudi Arabia/India) is the most frequent in this community, being present in 80.4% of the chromosomes tested; Benin haplotype 19 was found in 12.0% and Bantu haplotype 20 in 6.5%. Hb F in the haplotype 31 homozygotes and heterozygotes ranged from 11.4 to 35.1% (mean 22.5 ± 5.2%). The frequency of α-thal determinants in the study was 40.0%, the commonest being the -α3-7-kb deletion (27.5%), the α2 polyadenylation signal (AATAAA-> AATAAG) mutation (10.2%) and the IVS-I 5´ end GAGGT-GAGG-> GAGG pentanucleotide (5 nt) deletion (3.3%). SS patients with coexistent α-thal trait did not have severe recurrent infections and none had gallstones. The high frequencies of the Saudi Arabia/India βs haplotype and α-thalassemia trait contribute to the mild nature of SS disease among Kuwaiti Arabs comparable to that in eastern Saudi Arabia.

Using amplification, allele-specific oligonucleotide (ASO) hybridization and DNA sequencing we have documented the molecular basis of 64 α- and 123 β-thalassemia (thai) chromosomes, and the haplotypes of 18 β^s chromosomes from patients followed in three hospitals in Kuwait. Of the 30 chromosomes from 15 patients with Hb H disease, 26 (86.7%) carried the polyadenylation (poly A) signal mutation (AATAAA→AATAAG) in the α₂-globin gene, 3 (10%) had the -α (3.7 kb) deletion, and 1 (3.3%) had the pentanucleotide deletion in the 5´ IVS-I splice junction (α^-5ntα). As many as 12 different β-thal mutations were identified; 6 Mediterranean alleles [IVS-II-1 (G→A), IVS-I-6 (T→C), codon (CD) 39 (C→T), IVS-I-110 (G→A), CD 8 (-AA), and IVS-I-1 (G→A)] were present in 79 (64.2%) of the chromosomes tested. Four East Indian alleles [IVS-I-5 (G→C), IVS-I 3´ end -25 nt deletion, CDs 8/9 (+G), and 619-bp deletion] were found in 31 (25%), and the two Kurdish/Iranian alleles [CD 44 (-C) and CDs 36/37 (-T)] were found in 13 (10.6%) chromosomes. Fourteen β^s chromosomes carried haplotype No. 31 (Saudi Arabia/ India); 3 had haplotype No. 19 (Benin), and 1 was a hybrid with haplotype No. 31-specific characteristics in the locus control region hypersensitive site-2 (LCR-HS-2), and haplotype No. 19-specific mutations in the 5´ flanking region of the Gγ-promoter. The patient homozygous for haplotype No. 19 was a Jordanian, while the others were Kuwaiti Arabs. The latter appear to be fairly homogeneous in terms of the prevalent α-thal determinants and β^s-haplotypes, but there is considerable heterogeneity of their β-thal alleles. This has implications for genetic counseling and prenatal diagnosis programs.

Avascular necrosis (AVN) of the hip is a common cause of morbidity in sickle cell disease (SCD). Its prevalence increases with age and predisposing factors include coexistent α-thalassemia trait, frequent vaso-occlusive crisis and a high hematocrit (Hct). SCD is relatively mild among Kuwaiti patients because of their elevated Hb F levels, but a subset exists with severe recurrent vaso-occlusive crises. We carried out a prospective magnetic resonance imaging (MRI) study of the hip in a group of patients being followed in the Pediatric Hematology clinics of Al-Mubarak and Al-Amiri Hospitals. The association of AVN with age, frequency of hospitalization, α-thal trait, steady-state Hb, Hct, Hb F, WBC and platelet counts was investigated. MRI was carried out with a 1.5-tesla GE unit with a super-conducting magnet. Thirty patients (19 males, 11 females) (23 SS and 7 SβThal) were studied. Their ages ranged from 6 to 17 years, with a mean of 9.8 ± 3.5 years, and Hb F from 11 to 35% with a mean of 22.8 ± 5.7%. Among the SS patients, 11 (47.8%) had coexistent α-thal trait (–3.7-kb deletion). A total of 8 (26.7%) patients (6 SS and 2 SβThal) had varying degrees of osteonecrosis of the hip. Four (36.4%) of the 11 SS patients with α-thal trait and 2 (16.7%) of those without α-thal trait had osteonecrosis. This difference is, however, not statistically significant (χ² = 0.3, p = 0.5). While there was also no significant difference in the mean age and hematological parameters (Hb, Hct, Hb F, WBC, platelets), the SS patients with osteonecrosis had a significantly higher number of hospitalizations for vaso-occlusive crisis in the preceding 3 years than those without osteonecrosis.

To investigate the frequency of angiotensinconverting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in adults with psoriatic arthritis (PsA), a heterogeneous chronic disease with autoimmune pathology. ACE gene I/D polymorphism inXuences the plasma and tissue levels of ACE and has an involvement in inXammatory mechanism. The frequency of ACE gene I/D polymorphism genotypes was determined in 51 adults with PsA from Kuwait, and compared to that in 100 ethnically matched healthy controls using polymerase chain reaction. The distribution of ACE I/D polymorphism and allele frequencies in PsA patients were not signiWcantly diVerent from controls (P > 0.05). Further analyses of PsA patients showed that ACE I/D gene polymorphism was not associated with family history, clinical manifestations, and disease severity. However, the frequency of II genotype was signiWcantly higher in patients with late disease onset than in those with early onset (25 vs. 3%; P = 0.04). No diVerence was found between the distribution of the ACE genotype in PsA patients and the general population in Kuwait.However, the presence of II genotype may confer susceptibility to the development of late onset PsA.

The course and severity of systemic lupus erythematosus (SLE) in children is generally similar to the adult form with potential serious organ system involvement, there are, however, factors that influence the prevalence and clinical behavior of the disease. Our objective was to analyse the organ system involvement and immunological findings in Kuwaiti children with SLE in relation to gender and age of onset and compare these findings to that in published reports. Organ system involvement and serologic profiles were analysed in 35 children with SLE. The major organ systems studied were: renal, hematological, cardiac, pulmonary, hepatic and the central nervous system. The prevalence of ANA, anti-dsDNA, anti-Sm, SSA, SSB and anti-cardiolipin antibodies were studied in addition to complement C3 and C4 levels. The results showed that a high percentage of children had hematological involvement (34%); thrombocytopenia (23%) and hemolytic anemia (20%). Renal involvement was proven by biopsy in only 10 children (29%). Neuropsychiatric manifestations were seen in five (14%) of patients. Males had a tendency for major organ involvement relative to females. All patients had positive ANA tests. All males had positive anti-dsDNA tests compared to 86% of female patients. The most significant finding in this study is the high frequency of hematological manifestations and the relatively low incidence of renal disease and neuropsychiatric abnormalities in Kuwaiti children with SLE.

BackgroundType 1 diabetes mellitus (T1DM) is highly prevalent in Kuwait with incidence of around 40.1/100,000 individuals. Evidence indicate that vitamin D plays an important role in modulating the immune system and could thus impact the onset and high prevalence of T1DM. We report serum vitamin D levels in Kuwaiti children with T1DM and non-diabetic controls to explore its relationship with prevalence and onset of the disease.MethodsThis study included 216 Kuwaiti Arab children with T1DM. The diagnosis of T1DM was based on the ISPAD criteria. The control subjects (204 Kuwaitis) were age and gender matched, healthy, non-diabetic, and had no close relative with T1DM. Vitamin D levels were determined in serum using an enzyme immunoassay (EIA) method.ResultsThe age of onset of T1DM was <4y in 20 % of the T1DM cases, between 4 and 6y in 28 % cases and >6y in 52 % patients. In T1DM patient group, 84 % subjects were found to be deficient in serum vitamin D level compared to 77 % of the controls (p = 0.046). Collectively, the deficient and insufficient vitamin D status was detected in 99 % of the T1DM patients compared to 92 % of the controls (p = 0.027). The mean serum vitamin D levels were found to be significantly different in early onset cases (age <4y) compared to the late onset sub-group (p = 0.001). A significant correlation was found between some elements of socioeconomic status, SES (i.e. parent’s profession and family’s income) and lower vitamin D levels in Kuwaiti T1DM children. There was no significant difference between mean serum vitamin D levels during winter and summer months in the T1DM patients.ConclusionsThe proportion of cases with a deficient vitamin D status was significantly high in Kuwaiti T1DM children compared to the controls. The serum vitamin D levels were found to be significantly different in early onset and late onset T1DM patients. Therefore, serum vitamin D status can be considered an important contributor in high prevalence of T1DM in Kuwaiti children.

The prevalence of human leukocyte antigen (HLA) DQB1 and DQA1 alleles has been determined in 78 Kuwaiti Arab children with insulin-dependent diabetes mellitus (IDDM) and in 57 normal healthy controls with similar ethnic background. The typing of HLA-DQ alleles was carried out using an allele-specific DNA-based polymerase chain reaction (PCR) SSP method. DR typing was also performed in 212 control subjects using PCR-SSP (sequence specific primer) method. A significantly higher frequency of DQB1*0201 allele was found in IDDM cases compared to the controls (p<0.001). There was no significant difference in the prevalence of DQB1 alleles *0302, *0501, and *0602 between IDDM cases and the controls. In contrast, DQB1 alleles *0301, *0402, *0502, *0602, and *0603 were represented at a somewhat higher frequency in controls compared to the IDDM cohort. The frequency of DQA1 allele *0301, which encode for an Arg at codon 52, was significantly higher in the IDDM patients compared to the controls (p<0.001). The frequency of DQA1 allele *0302 was also higher in IDDM cases than controls (p = 0.034) but the difference was less pronounced than DQA1*0301. Amongst the Arg52 alleles, no significant difference was detected in the frequency of *0401 between IDDM cases and the controls and the allele *0501 was detected only in controls. For non-Arg52 alleles *0103, *0104, and *0201, the differences in the two groups were not significant, with the exception of allele *0104 (p = 0.024). DR3 was the most common type in the Kuwaiti general population (28%) and DRB1*0301 was detected in 41% of the individuals with DR3 specificity. Analysis of HLA-DQBI/DQA1 haplotypes from IDDM cases and controls revealed a significantly high frequency of haplotype DQA1*0301/DQB1*0201 between Kuwaiti IDDM cases (49/78, 63%) and the controls (8/57, 14%).

Low back pain (LBP) is a common medical problem. Interaction between genetic and environmental factors predisposes individuals to LBP even at an early age. Inflammatory back pain or spondylarthropathies include ankylosing spondylitis (AS), psoriatic arthritis (PSA), reactive arthritis enteropathic and undifferentiated arthropathies. Angiotensin-converting enzyme (ACE) plays an important role in circulatory homeostasis, physiology of vasculature and inflammation. The insertion-deletion (I/D) polymorphism of the ACE gene has been shown to determine the plasma and tissue levels of ACE especially in the synovial fluid. The aim of this study was to investigate an association between ACE gene I/D polymorphism and inflammatory back pain (spondylarthropathies) secondary to ankylosing spondylitis (AS), psoriatic arthritis, inflammatory bowel disease and undifferentiated spondylarthropathies. The prevalence of ACE gene I/D polymorphism genotypes was determined in 63 patients with inflammatory back pain by polymerase chain reaction (PCR) and compared with that in 111 healthy controls. Of the 63 patients studied, 45 (71.4%) were with AS, 13 (20.6%) were with PSA, 4 (6.3%) were with reactive arthropathy and 1 (1.6%) manifested undifferentiated arthropathy. There were 43 males and 20 females. Mean age of patients was 39.0+/-11.36 years, age at onset of spondylarthropathy was 27.7+/-7.49 years and disease duration was 10.3+/-7.74 months. The controls were selected to match with the patients group in terms of gender ratio, age and ethnicity. The ACE gene polymorphism showed an overall significant difference between patients and controls (p=0.050). When the ID and II genotype frequency was combined and compared with that for DD genotype amongst patient and control groups, a considerably higher incidence was detected for ID and II genotypes than the DD genotype in spondylarthropathy patients compared to that in the controls (p=0.036). This study showed a significant association of the I-allele of ACE gene I/D polymorphism with spondylarthropathy in Kuwaiti Arabs.