• Renata Mojzikova, Pavla Koralkova, Dusan Holub, Zuzana Zidova, Dagmar Pospisilova, Jaroslav Cermak, Zuzana Striezencova Laluhova, Karel Indrak, Martina Sukova, Martina Partschova, Jana Kucerova, Monika Horvathova, and Vladimir Divoky.
• Department of Biology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
• Br. J. Haematol. 2014 May 1; 165 (4): 556-63.

AbstractPyruvate 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. © 2014 John Wiley & Sons Ltd.

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