Sickle Cell Disease Subphenotypes in Patients From Southwestern Province of Saudi Arabia

Abstract

Sickle cell disease (SCD) is common in the Eastern and Southwestern (SW) Provinces of Saudi Arabia. We studied 159 patients with SCD to better characterize its phenotype in the SW Province, where patients usually have a HBB haplotype of African origin. All cases had history and examination, chart review, and laboratory testing. Blood tests were obtained during steady state and included: complete blood count, reticulocytes, hemoglobin electrophoresis, lactate dehydrogenase, and G6PD level. HBB haplotype and presence of α-thalassemia were also determined. Frequency of various SCD complications was as follows: painful episodes of variable severity occurred in majority of patients (98%), osteonecrosis (14%), acute chest syndrome (22%), splenic sequestration (23%), gallstones (34%), stroke (7.5%), priapism (2.6%), serious infections (11.5%), and persistent splenomegaly (11%) beyond 5 years of age. No patient had leg ulcer. History of asthma and high steady state white blood cells count were associated with increased risk of acute chest syndrome. Coinheritance of α-thalassemia was associated with a lower frequency of gallstones. Higher fetal hemoglobin level was associated with persistent splenomegaly but not with other complications. Splenic sequestration was more common among males and was associated with lower steady state hemoglobin. SCD phenotype in the SW Province is variable and comparable with African Americans except for the rarity of priapism and the absence of leg ulcers. Fetal hemoglobin level was not associated with SCD vaso-occlusive complications. New genetic modifiers and environmental factors might modulate the phenotype of SCD in Saudi Arabia.

A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease

“…However, some HbF remains to be heterogeneously transcribed with variable expression levels across HbF red blood cells (F cells) [32]. Initial observations suggested that HBB haplotypes also have an effect on the severity of SCD [8,9]. The Bantu haplotype being the less favourable and the Indian-Arab haplotype associated to the least severity; as the latter is associated with higher HbF levels [33], due to a single nucleotide polymorphism (SNP) upstream of the β-globin gene (rs7482144 or Xmn- G γ), characteristically present in Indian Arab and Senegal haplotypes [34].…”

“…Four haplotypes are associated with HbS in Africa (Benin, Bantu/Central African Republic (CAR), Senegal and Cameroon) and the fifth is thought to have arisen in India and/or the Arabian Peninsula (Arab/Hindu) [6,7]. It has been suggested that these haplotypes also have an effect on the severity of the disease through their genetically-determined effect on HbF level [8,9]. …”

Differences in the clinical and genotypic presentation of sickle cell disease around the world

“…High rates of α-thalassemia are also observed in the Middle East with estimates of up to 50% of the population carrying deletional (−α 3.7 and −α 4.2 ) or nondeletional (α Constant Spring and α TSaudi ) forms of α-thalassemia (36). In cohorts of Hb SS populations from the Middle East, frequencies of the (−α) chromosome are 0.39 – 0.48 (37, 38). Migration patterns have led to the distribution of α-thalassemia deletion and non-deletion mutations in non-malaria endemic regions.…”

Contribution of Reduced Interleukin-10 Levels to the Pathogenesis of Osteomyelitis in Children with Sickle Cell Disease

“…ickle cell disease (SCD) is a monogenic, inherited anemia with variable clinical manifestations and associated variable disease severity (1), since some patients present with severe complications, while others do not present with any SCD complications (2). Besides vasoocclusive crisis (VOC), osteomyelitis is a common complication of SCD and is a major cause for hospitalization of SCD patients (3).…”