title: Erythrocyte pyruvate kinase deficiency in an old-order Amish cohort: longitudinal risk and disease management.
abstract: Pyruvate kinase deficiency is a chronic illness with age specific consequences. Newborns suffer life-threatening hemolytic crisis and hyperbilirubinemia. Adults are at risk for infections because of asplenia, pregnancy-related morbidity, and may suffer organ damage because of systemic iron overload. We describe 27 Old Order Amish patients (ages 8 months-52 years) homozygous for c.1436G>A mutations in PKLR. Each subject had a predictable neonatal course requiring packed red blood cell transfusions (30 ± 5 mL/kg) to control hemolytic disease and intensive phototherapy to prevent kernicterus. Hemochromatosis affected 29% (n = 4) of adult patients, who had inappropriately normal serum hepcidin (34.5 ± 12.7 ng/mL) and GDF-15 (595 ± 335pg/mL) relative to hyperferritinemia (769 ± 595 mg/dL). A high prevalence of HFE gene mutations exists in this population and may contribute to iron-related morbidity. Based on our observations, we present a strategy for long-term management of pyruvate kinase deficiency.
authors.affiliation: Clinic for Special Children, Strasburg, Pennsylvania, PA 17579, USA. nrider@clinicforspecialchildren.org
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Rider
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.forename: Krysta
authors.initials: K
authors.lastname: Brown
authors.forename: Armin
authors.initials: A
authors.lastname: Finkenstedt
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
authors.forename: Christine L
authors.initials: CL
authors.lastname: Hendrickson
authors.forename: Donna L
authors.initials: DL
authors.lastname: Robinson
authors.forename: Nikolas
authors.initials: N
authors.lastname: Muenke
authors.forename: Chris
authors.initials: C
authors.lastname: Tselepis
authors.forename: Lauren
authors.initials: L
authors.lastname: Saunders
authors.forename: Heinz
authors.initials: H
authors.lastname: Zoller
authors.forename: D Holmes
authors.initials: DH
authors.lastname: Morton
mesh_terms: D000293:Adolescent; D000328:Adult; D061365:Amish; D000743:Anemia, Hemolytic / Q000097:blood / Q000201:enzymology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019468:Disease Management; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010414:Pennsylvania; D011247:Pregnancy; D011770:Pyruvate Kinase / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult
chemical_list: D011770:Pyruvate Kinase