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Genotype-phenotype correlation in children with hereditary spherocytosis.
British journal of haematology
  • Soumitra Tole, Western University
  • Priya Dhir, University of Toronto
  • Jakob Pugi, Hospital for Sick Children, Toronto
  • Luke J. Drury, PreventionGenetics
  • Sheila Butchart, Hospital for Sick Children, Toronto
  • Michelle Fantauzzi, Hospital for Sick Children, Toronto
  • Jacob C. Langer, Hospital for Sick Children, Toronto
  • Jillian M. Baker, University of Toronto
  • Victor S. Blanchette, Hospital for Sick Children, Toronto
  • Melanie Kirby-Allen, Hospital for Sick Children, Toronto
  • Manuel D. Carcao, Hospital for Sick Children, Toronto
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Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed a retrospective study of 166 children with HS and describe the clinical phenotype according to the genotype. In 160/166 (97%) children with HS a disease-causing mutation was identified. Pathogenic variants in ANK1, SPTB, SLC4A1 and SPTA1 were found in 49%, 33%, 13% and 5% of patients. Children with SLC4A1-HS had the mildest phenotype, showing the highest haemoglobin (P < 0·001), lowest reticulocyte counts (P < 0·001) and lowest unconjugated bilirubin levels (P = 0·006), and none required splenectomy in childhood (P < 0·001). Conversely, children with autosomal recessive SPTA1-HS had the most severe clinical phenotype, with almost all patients undergoing splenectomy in early childhood. Patients with ANK1 and SPTB variants showed a similar clinical phenotype. Within each gene, variant type or location did not predict disease severity or likelihood of splenectomy. Among patients with a genetic diagnosis, 47 (29%) underwent splenectomy (23 partial; 24 total) while 57 (36%) underwent cholecystectomy. Total splenectomy led to greater improvements in haemoglobin (P = 0·02). Select use of genetic testing (especially in patients without a family history) may help predict clinical phenotype in childhood and guide family counselling.


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Citation Information
Soumitra Tole, Priya Dhir, Jakob Pugi, Luke J. Drury, et al.. "Genotype-phenotype correlation in children with hereditary spherocytosis." British journal of haematology Vol. 191 Iss. 3 (2020) p. 486 - 496
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