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
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24533562
DOI
10.1111/bjh.12779
Knihovny.cz E-resources
- Keywords
- ferritin, hepcidin, iron overload, pyruvate kinase deficiency, red blood cell,
- MeSH
- Child MeSH
- Adult MeSH
- Erythropoiesis MeSH
- Ferritins blood MeSH
- Anemia, Hemolytic, Congenital Nonspherocytic blood genetics MeSH
- Hepcidins biosynthesis blood MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Molecular Sequence Data MeSH
- Mutation * MeSH
- DNA Mutational Analysis MeSH
- Infant, Newborn MeSH
- Transfusion Reaction MeSH
- Child, Preschool MeSH
- Iron Overload genetics MeSH
- Pyruvate Kinase blood deficiency genetics MeSH
- Amino Acid Sequence MeSH
- Sequence Analysis, DNA MeSH
- Pyruvate Metabolism, Inborn Errors blood genetics MeSH
- Iron blood MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Ferritins MeSH
- HAMP protein, human MeSH Browser
- Hepcidins MeSH
- Pyruvate Kinase MeSH
- Iron MeSH
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.
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