Andreas Glenthøj, Rachael F. Grace, Carl Lander, Eduard J. van Beers, Bertil Glader, Kevin H. M. Kuo, Yan Yan, Bryan McGee, Audra N. Boscoe, Junlong Li, Paola Bianchi
Copenhagen University Hospital – Rigshospitalet. Dana-Farber/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School. Thrive with PK Deficiency. University Medical Center Utrecht and Utrecht University. Stanford University School of Medicine. University of Toronto.
Agios Pharmaceuticals. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico.
Denmark, United States, Netherlands, Canada and Italy
British Journal of Haematology
Brit J Haematol 2024; 205: 613-623
10.1111/bjh.19601
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.
Category
Class V. Pulmonary Hypertension Associated with Hematological, Systemic, Metabolic and Other Disorders
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes