Sickle Cell Disease—Genetics, Pathophysiology, Clinical Presentation and Treatment

Abstract

Sickle cell disease (SCD) is a monogenetic disorder due to a single base-pair point mutation in the β-globin gene resulting in the substitution of the amino acid valine for glutamic acid in the β-globin chain. Phenotypic variation in the clinical presentation and disease outcome is a characteristic feature of the disorder. Understanding the pathogenesis and pathophysiology of the disorder is central to the choice of therapeutic development and intervention. In this special edition for newborn screening for haemoglobin disorders, it is pertinent to describe the genetic, pathologic and clinical presentation of sickle cell disease as a prelude to the justification for screening. Through a systematic review of the literature using search terms relating to SCD up till 2019, we identified relevant descriptive publications for inclusion. The scope of this review is mainly an overview of the clinical features of pain, the cardinal symptom in SCD, which present following the drop in foetal haemoglobin as young as five to six months after birth. The relative impact of haemolysis and small-vessel occlusive pathology remains controversial, a combination of features probably contribute to the different pathologies. We also provide an overview of emerging therapies in SCD.

Laparoscopic cholecystectomy in children with sickle cell disease: A simple modified technique

“…However, patients with sickle cell disease require special perioperative care to optimize the patient for surgery and minimize the incidence of sickle cell disease-related complications. 14,15 Perioperative care includes performing a simple blood or exchange transfusion, maintaining adequate hydration and oxygenation in the patient, keeping the patient warm, maintaining an acid-base balance, and administering prophylactic antibiotics. 15 Laparoscopic cholecystectomy has been the gold standard for gallbladder removal since 1989.…”

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“…6 Persistent haemolysis and acute vasocclusive painful crises are the most common type of crisis with the prevalence of cerebrovascular accidents 3 (4%) Acute pain episodes occurred in SCD patients are described as one of the most excruciating forms of pain affect the human beings. 2,7 It is caused by microvascular occlusion which lead to stimulation of nociceptive nerve fibers, moreover, microvascular occlusion can result in ischemia, edema, necrosis, and organ damage. 2 Pain can occur in the abdomen, bones, joints, or muscles.…”

“…2,7 It is caused by microvascular occlusion which lead to stimulation of nociceptive nerve fibers, moreover, microvascular occlusion can result in ischemia, edema, necrosis, and organ damage. 2 Pain can occur in the abdomen, bones, joints, or muscles. Young children often present with pain involving the hands or feet (the hand-foot syndrome or dactylitis), long bones and the abdomen are more common sites of pain in adults.…”

Genetic Polymorphisms of HBS1L-MYB (rs4895441 and rs9376090) in Egyptian Patients with Hemoglobinopathy

“…In Africa, more than 200,000 infants are born yearly with sickle cell anemia [6]. Sickle cell disease is an inherited genetic disorder, resulting from homozygous and compound heterozygote mutation in the β globin gene as a single base-pair point mutation (GAG to GTG) results in the substitution of glutamic acid (hydrophilic) to Valine (hydrophobic) in the 6 th position of the β-chain of hemoglobin resulting in hemoglobin S formation [7].…”

“…Disturbance in the interval between the HBS1L and MYB suppresses MYB expression and gives rise to the increased level of Hb F [7]. Single nucleotide polymorphisms (SNPs) in the Gγ-globin gene promoter in BCL11A regions and HBS1L-MYB intergenic polymorphism (HMIP) are thought to be associated with Hb F levels.…”