Health-Related Quality of Life and Fatigue in Children and Adults with Pyruvate Kinase Deficiency.

Pyruvate kinase deficiency (PKD) is the most common cause of congenital non-spherocytic hemolytic anemia. Although recognition of the disease spectrum has recently expanded, data describing its impact on health-related quality of life (HRQoL) are limited. In this prospective international cohort of 254 patients (131 adults and 123 children) with PKD, we assessed the disease impact on HRQoL (EuroQL-5D, PedsQL, FACT-An) and fatigue (PROMIS Fatigue, PedsFACIT-F) using validated measures. Significant variability in HRQoL and fatigue was reported for both adults and children although individual scores were stable over a 2-year interval. While adults who were regularly transfused reported worse HRQoL and fatigue compared to those who were not regularly transfused (EQ-VAS 58 vs. 80, p=0.01), this difference was not seen in children. Regularly transfused adults reported lower physical, emotional, and functional well-being and more anemia symptoms. Both HRQoL and fatigue significantly differed in children by genotype with the worst scores in those with two severe PKLR mutations; this difference was not seen in adults. However, iron chelation was associated with significantly worse HRQoL scores in both children and adults. Pulmonary hypertension was also associated with significantly worse HRQoL. In PKD-specific symptom assessment, 59% of adults and 35% of children reported that their jaundice upset them, identifying this as an important symptom for consideration. While current treatments for PK deficiency are limited to supportive care, new therapies are currently in clinical trials. Understanding the impact of PKD on HRQoL is important to assess the utility of these treatments. (Clinicaltrials.gov number NCT02053480).