title: Iron status in patients with pyruvate kinase deficiency: neonatal hyperferritinaemia associated with a novel frameshift deletion in the PKLR gene (p.Arg518fs), and low hepcidin to ferritin ratios.
abstract: Pyruvate kinase (PK) deficiency is an iron-loading anaemia characterized by chronic haemolysis, ineffective erythropoiesis and a requirement for blood transfusion in most cases. We studied 11 patients from 10 unrelated families and found nine different disease-causing PKLR mutations. Two of these mutations - the point mutation c.878A>T (p.Asp293Val) and the frameshift deletion c.1553delG (p.(Arg518Leufs*12)) - have not been previously described in the literature. This frameshift deletion was associated with an unusually severe phenotype involving neonatal hyperferritinaemia that is not typical of PK deficiency. No disease-causing mutations in genes associated with haemochromatosis could be found. Inappropriately low levels of hepcidin with respect to iron loading were detected in all PK-deficient patients with increased ferritin, confirming the predominant effect of accelerated erythropoiesis on hepcidin production. Although the levels of a putative hepcidin suppressor, growth differentiation factor-15, were increased in PK-deficient patients, no negative correlation with hepcidin was found. This result indicates the existence of another as-yet unidentified erythroid regulator of hepcidin synthesis in PK deficiency.
authors.affiliation: Department of Biology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Mojzikova
authors.forename: Pavla
authors.initials: P
authors.lastname: Koralkova
authors.forename: Dusan
authors.initials: D
authors.lastname: Holub
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zidova
authors.forename: Dagmar
authors.initials: D
authors.lastname: Pospisilova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Striezencova Laluhova
authors.forename: Karel
authors.initials: K
authors.lastname: Indrak
authors.forename: Martina
authors.initials: M
authors.lastname: Sukova
authors.forename: Martina
authors.initials: M
authors.lastname: Partschova
authors.forename: Jana
authors.initials: J
authors.lastname: Kucerova
authors.forename: Monika
authors.initials: M
authors.lastname: Horvathova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Divoky
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000097:blood / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004920:Erythropoiesis; D005260:Female; D005293:Ferritins / Q000097:blood*; D064451:Hepcidins / Q000096:biosynthesis / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007501:Iron / Q000097:blood*; D019190:Iron Overload / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011770:Pyruvate Kinase / Q000097:blood / Q000172:deficiency* / Q000235:genetics*; D015323:Pyruvate Metabolism, Inborn Errors / Q000097:blood / Q000235:genetics*; D017422:Sequence Analysis, DNA; D065227:Transfusion Reaction; D055815:Young Adult
chemical_list: C578702:HAMP protein, human; D064451:Hepcidins; D005293:Ferritins; D007501:Iron; D011770:Pyruvate Kinase
keywords: ferritin; hepcidin; iron overload; pyruvate kinase deficiency; red blood cell