The clinical spectrum of pyruvate kinase deficiency: data from the Pyruvate Kinase Deficiency Natural History Study

UMMS Affiliation

Department of Pediatrics, Division of Hematology Oncology

Publication Date


Document Type



Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Hematology | Hemic and Lymphatic Diseases | Pediatrics


An international, multicenter registry was established to collect retrospective and prospective clinical data on patients with pyruvate kinase (PK) deficiency, the most common glycolytic defect causing congenital non-spherocytic hemolytic anemia. Medical history and laboratory and radiologic data were retrospectively collected at enrollment in 254 patients with molecularly confirmed PK deficiency. Perinatal complications were common, including anemia requiring transfusions, hyperbilirubinemia, hydrops, and prematurity. Nearly all newborns were treated with phototherapy (93%) with many treated with exchange transfusions (46%). Young children, < /=5 years old, were often transfused until splenectomy. Splenectomy, reported for 150/254 (59%) patients, was associated with a median rise in hemoglobin of 1.6 g/dl and a decreased transfusion burden in 90% of patients. Predictors of a response to splenectomy included: higher pre-splenectomy hemoglobin (p=0.007), lower indirect bilirubin (p=0.005), and missense PKLR mutations (p=0.0017). Post-splenectomy thrombosis was reported in 11% of patients. The most frequent complications included iron overload (48%) and gallstones (45%); however, other complications, such as aplastic crises, osteopenia/bone fragility, extramedullary hematopoiesis, post-splenectomy sepsis, pulmonary hypertension, and leg ulcers, were not uncommon. Overall, 87/254 (34%) patients had both a splenectomy and cholecystectomy. In those who had a splenectomy without simultaneous cholecystectomy, 48% later required a cholecystectomy. Although the risk of complications increases with severity of anemia and a genotype-phenotype relationship was observed, complications were common in all patients with PK deficiency. Diagnostic testing for PK deficiency should be considered in patients with apparent congenital hemolytic anemia and close monitoring for iron overload, gallstones, and other complications is needed regardless of baseline hemoglobin.

DOI of Published Version



Blood. 2018 Mar 16. pii: blood-2017-10-810796. doi: 10.1182/blood-2017-10-810796. Link to article on publisher's site

Journal/Book/Conference Title



Full list of authors omitted for brevity. For full list see article.

Related Resources

Link to Article in PubMed

PubMed ID