Adekile Adekunle D
Department of Pediatrics, Kuwait University, Jabriyah, Kuwait.
Hemoglobin. 2011;35(5-6):607-17. doi: 10.3109/03630269.2011.617230. Epub 2011 Oct 14.
Sickle cell disease is characterized by phenotypic heterogeneity and many genetic modifiers have been identified with elevated Hb F being the most recognized ameliorating factor. Kuwaiti sickle cell disease patients carry the India/Arab chromosomal haplotype, which is associated with elevated Hb F (on average 22%) on account of the Xmn1 site in the (G)γ-globin gene promoter. Most patients had either Hb SS or Hb S-β(0)-thalassemia (β(0)-thal) and there are a few Hb SD compound heterozygotes. We have carried out longitudinal clinical studies of these patients to document the pattern of morbidity, spleen function, brain and hip magnetic resonance imaging (MRI) for prevalence of silent brain infarcts and avascular necrosis of the femoral head (AVNFH), respectively. In addition, pulmonary function, SPECT (single photon emission computerized tomography) brain cerebral blood flow and response of selected patients to hydroxyurea (HU) treatment were also studied. The Hb SS and Hb S-β-thal patients have a generally mild phenotype compared to sickle cell disease in other populations and most patients do not have their first pain crisis until about the age of 4 years. Spleen function is retained till late childhood; pneumococcemia and other severe bacterial infections are rare. Overt stroke and silent brain infarcts are uncommon in childhood (3% prevalence) although SPECT reveals cerebral blood flow deficits in ~30%. Avascular necrosis of the femoral head is, however, common with a prevalence of ~26% in children and 50% in adults. There is brisk response to HU in patients with frequent pain crises, with marked increases in Hb F levels. Patients who are compound heterozygotes for Hbs S and D-Los Angeles, have the most severe phenotype despite Hb F levels of >20% and Hb S <30%. In conclusion, although the patients have a uniformly elevated Hb F level, there are still considerable phenotypic heterogeneity and other modulating genetic factors that require further studies.
镰状细胞病具有表型异质性，已鉴定出许多基因修饰因子，其中血红蛋白F（Hb F）升高是最公认的改善因素。科威特镰状细胞病患者携带印度/阿拉伯染色体单倍型，由于（G）γ-珠蛋白基因启动子中的Xmn1位点，该单倍型与Hb F升高（平均约22%）相关。大多数患者为Hb SS或Hb S-β（0）-地中海贫血（β（0）-地贫），还有少数Hb SD复合杂合子。我们对这些患者进行了纵向临床研究，以记录发病模式、脾脏功能、脑和髋部磁共振成像（MRI），分别用于检测无症状脑梗死和股骨头缺血性坏死（AVNFH）的患病率。此外，还研究了肺功能、单光子发射计算机断层扫描（SPECT）脑血流以及部分患者对羟基脲（HU）治疗的反应。与其他人群的镰状细胞病相比，Hb SS和Hb S-β-地贫患者的表型通常较轻，大多数患者直到4岁左右才首次出现疼痛危机。脾脏功能一直保留到儿童晚期；肺炎球菌血症和其他严重细菌感染很少见。儿童期明显的中风和无症状脑梗死并不常见（患病率约为3%），尽管SPECT显示约30%的患者存在脑血流不足。然而，股骨头缺血性坏死很常见，儿童患病率约为26%，成人患病率为50%。频繁疼痛危机的患者对HU反应迅速，Hb F水平显著升高。Hb S和D-洛杉矶复合杂合子患者，尽管Hb F水平>20%且Hb S<30%，但其表型最为严重。总之，尽管患者的Hb F水平均升高，但仍存在相当大的表型异质性和其他调节基因因素，需要进一步研究。
