Comorbidities and complications in adult and paediatric patients with pyruvate kinase deficiency: Analysis from the Peak Registry

Br J Haematol. 2024 Aug;205(2):613-623. doi: 10.1111/bjh.19601. Epub 2024 Jun 21.

Abstract

Pyruvate kinase (PK) deficiency, a rare, congenital haemolytic anaemia caused by mutations in the PKLR gene, is associated with many clinical manifestations, but the full disease burden has yet to be characterised. The Peak Registry (NCT03481738) is an observational, longitudinal registry of adult and paediatric patients with PK deficiency. Here, we described comorbidities and complications in these patients by age at most recent visit and PKLR genotype. As of 13 May 2022, 241 patients were included in the analysis. In total, 48.3% had undergone splenectomy and 50.5% had received chelation therapy. History of iron overload (before enrolment/during follow-up) was common (52.5%), even in never-transfused patients (20.7%). Neonatal complications and symptoms included jaundice, splenomegaly and hepatomegaly, with treatment interventions required in 41.5%. Among adults, osteopenia/osteoporosis occurred in 19.0% and pulmonary hypertension in 6.7%, with median onset ages of 37, 33 and 22 years, respectively. Biliary events and bone health problems were common across PKLR genotypes. Among 11 patients who had thromboembolic events, eight had undergone prior splenectomy. Patients with PK deficiency may have many complications, which can occur early in and throughout life. Awareness of their high disease burden may help clinicians better provide appropriate monitoring and management of these patients.

Keywords: adult and paediatric haematology; haemolytic anaemia; iron–clinical iron overload; pyruvate kinase deficiency; red cells–enzyme disorders.

Publication types

  • Observational Study
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Hemolytic, Congenital Nonspherocytic* / epidemiology
  • Anemia, Hemolytic, Congenital Nonspherocytic* / genetics
  • Bone Diseases, Metabolic / epidemiology
  • Bone Diseases, Metabolic / etiology
  • Child
  • Child, Preschool
  • Comorbidity
  • Female
  • Humans
  • Hypertension, Pulmonary / epidemiology
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / genetics
  • Infant
  • Infant, Newborn
  • Iron Overload / epidemiology
  • Iron Overload / etiology
  • Male
  • Middle Aged
  • Pyruvate Kinase* / deficiency
  • Pyruvate Kinase* / genetics
  • Pyruvate Metabolism, Inborn Errors* / epidemiology
  • Pyruvate Metabolism, Inborn Errors* / genetics
  • Registries*
  • Splenectomy
  • Young Adult

Substances

  • Pyruvate Kinase
  • PKLR protein, human

Supplementary concepts

  • Pyruvate Kinase Deficiency of Red Cells