sickle cell disease (SCD)

RCH guideline - sickle cell disease

introduction

sickle cell disease is a hereditary autosomal dominant haemoglobinopathy due to homozygous HbS which usually presents in childhood
the gene is present in 8% (2 million) of black Americans who thus have sickle cell trait but only 30,000 have homozygous HbS, thus sickle cell disease occurs in 1 in 500 African Americans
sickle cell trait is high in parts of Africa (reaching 30% is some areas) and other regions where malaria is endemic (Sicily, Greece, southern Turkey, and India) as sickle cell trait offers survival benefit in malaria prone regions.
the HbS gene has only one amino acid difference from the normal HbA gene

clinical features

painful vaso-occlusive crises
- the most common and most distinguishing clinical manifestation of SCD
- triggered by:
  - hypoxia
  - dehydration and acidosis
  - changes in body temperature
acute and chronic pain in any body part due to infarctions
- bone pain from infarction of marrow
- hand-foot syndrome
  - dactylitis presenting as bilateral painful and swollen hands and/or feet in children
- avascular necrosis of the femoral or humeral head
- chronic leg ulcers
chronic, haemolytic anaemia
- cholelithiasis (gallstones) is common in children
functional hyposplenism
- high risk of invasive pneumococcal disease and infections by other encapsulated bacteria
- dult infections are predominately with gram-negative organisms, especially Salmonella
aplastic crisis
- serious complication due to infection with B19V
splenic sequestration
- onset of life-threatening anemia with rapid enlargement of the spleen and high reticulocyte count
growth retardation, delayed sexual maturation, being underweight
acute chest syndrome:
- young children present with chest pain, fever, cough, tachypnea, leukocytosis, and pulmonary infiltrates in the upper lobes
- adults are usually afebrile, SOB with severe chest pain, with multilobar/lower lobe disease
pulmonary hypertension
stroke (CVA)
eye: ptosis, retinal vascular changes, proliferative retinitis
urologic:
- kidneys lose concentrating capacity
  - median age at the time of renal failure in patients with SCD is 23 years
  - median survival time after the diagnosis of ESRD is about 4 years
  - median age of death is 27 years, despite dialysis treatment
- priapism is a well-recognized complication

genetic Rx

in 2019, CRISPR DNA editing technology was used to replace HbS gene with HbF gene in bone marrow cells which were then transfused back into the patient after her bone marrow red cell precursors were wiped out ¹⁾

¹⁾

https://www.news-medical.net/news/20190730/First-ever-American-gene-editing-treatment-using-CRISPR-for-genetic-disease.aspx

Table of Contents

sickle cell disease (SCD)

introduction

clinical features

genetic Rx