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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
Author(s) -
Mojzikova Renata,
Koralkova Pavla,
Holub Dusan,
Zidova Zuzana,
Pospisilova Dagmar,
Cermak Jaroslav,
Striezencova Laluhova Zuzana,
Indrak Karel,
Sukova Martina,
Partschova Martina,
Kucerova Jana,
Horvathova Monika,
Divoky Vladimir
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12779
Subject(s) - hepcidin , frameshift mutation , pyruvate kinase deficiency , erythropoiesis , ineffective erythropoiesis , ferritin , biology , medicine , iron deficiency , pyruvate kinase , endocrinology , mutation , point mutation , gene , anemia , genetics , metabolism , glycolysis
Summary 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.