Red cell pyruvate kinase deficiency in Spain: A study of 15 cases

Med Clin (Barc). 2017 Jan 6;148(1):23-27. doi: 10.1016/j.medcli.2016.10.004. Epub 2016 Nov 19.
[Article in English, Spanish]

Abstract

Background and objective: Pyruvate kinase deficiency (PKD) is a rare, inherited disease causing chronic hemolysis and anemia of varying intensity. The genetic heterogeneity of PKD is high and, to this day, over 240 different mutations have been identified.

Patients and methods: 15 unrelated patients affected by PKD have been studied. PKLR gene sequencing was performed by SANGER, including the determination of promoter regions, exonic, intronic flanking and 3'UTR.

Results: Patients were classified into 3 groups based on the intensity of their clinical symptoms: I) severe and very severe (8 patients); II) moderate (2 patients), and III) mild (5 patients). Six out of the 18 alleles found were new mutations which had not been described previously, with the PKLR c.721G>T mutation being the most prevalent (26.67%), followed by the PKLR c.1456C>T mutation (13.33%).

Conclusions: In Spain, the genetic heterogeneity of PKLR is still high but differs from that observed in the previous study carried out in 1998. Total PKLR gene sequencing is necessary for the characterization of all patients with PKD and for genetic counseling.

Keywords: Anemia hemolítica crónica; Chronic hemolytic anemia; Déficit de piruvato cinasa; Genetic sequencing; Molecular variants; Pyruvate kinase deficiency; Secuenciación genética; Variantes moleculares.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Hemolytic, Congenital Nonspherocytic / diagnosis
  • Anemia, Hemolytic, Congenital Nonspherocytic / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genetic Markers
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation*
  • Pyruvate Kinase / deficiency*
  • Pyruvate Kinase / genetics*
  • Pyruvate Metabolism, Inborn Errors / diagnosis
  • Pyruvate Metabolism, Inborn Errors / genetics*
  • Severity of Illness Index
  • Spain
  • Young Adult

Substances

  • Genetic Markers
  • Pyruvate Kinase

Supplementary concepts

  • Pyruvate Kinase Deficiency of Red Cells