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The pyruvate kinase (PK) to hexokinase enzyme activity ratio and erythrocyte PK protein level in the diagnosis and phenotype of PK deficiency.

Publication ,  Journal Article
Al-Samkari, H; Addonizio, K; Glader, B; Morton, DH; Chonat, S; Thompson, AA; Kuo, KHM; Ravindranath, Y; Wang, H; Rothman, JA; Kwiatkowski, JL ...
Published in: Br J Haematol
March 2021

Diagnosis of pyruvate kinase deficiency (PKD), the most common cause of hereditary non-spherocytic haemolytic anaemia, remains challenging in routine practice and no biomarkers for clinical severity have been characterised. This prospective study enrolled 41 patients with molecularly confirmed PKD from nine North American centres to evaluate the diagnostic sensitivity of pyruvate kinase (PK) enzyme activity and PK:hexokinase (HK) enzyme activity ratio, and evaluate the erythrocyte PK (PK-R) protein level and erythrocyte metabolites as biomarkers for clinical severity. In this population not transfused for ≥90 days before sampling, the diagnostic sensitivity of the PK enzyme assay was 90% [95% confidence interval (CI) 77-97%], whereas the PK:HK ratio sensitivity was 98% (95% CI 87-100%). There was no correlation between PK enzyme activity and clinical severity. Transfusion requirements correlated with normalised erythrocyte ATP levels (r = 0·527, P = 0·0016) and PK-R protein levels (r = -0·527, P = 0·0028). PK-R protein levels were significantly higher in the never transfused [median (range) 40·1 (9·8-73·9)%] versus ever transfused [median (range) 7·7 (0·4-15·1)%] patients (P = 0·0014). The PK:HK ratio had excellent sensitivity for PK diagnosis, superior to PKLR exon sequencing. Given that the number of PKLR variants and genotype combinations limits prognostication based on molecular findings, PK-R protein level may be a useful prognostic biomarker of disease severity and merits further study.

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Published In

Br J Haematol

DOI

EISSN

1365-2141

Publication Date

March 2021

Volume

192

Issue

6

Start / End Page

1092 / 1096

Location

England

Related Subject Headings

  • Severity of Illness Index
  • Pyruvate Metabolism, Inborn Errors
  • Pyruvate Kinase
  • Middle Aged
  • Male
  • Infant
  • Immunology
  • Humans
  • Hexokinase
  • Female
 

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Al-Samkari, H., Addonizio, K., Glader, B., Morton, D. H., Chonat, S., Thompson, A. A., … Grace, R. F. (2021). The pyruvate kinase (PK) to hexokinase enzyme activity ratio and erythrocyte PK protein level in the diagnosis and phenotype of PK deficiency. Br J Haematol, 192(6), 1092–1096. https://doi.org/10.1111/bjh.16724
Al-Samkari, Hanny, Kathryn Addonizio, Bertil Glader, D Holmes Morton, Satheesh Chonat, Alexis A. Thompson, Kevin H. M. Kuo, et al. “The pyruvate kinase (PK) to hexokinase enzyme activity ratio and erythrocyte PK protein level in the diagnosis and phenotype of PK deficiency.Br J Haematol 192, no. 6 (March 2021): 1092–96. https://doi.org/10.1111/bjh.16724.
Al-Samkari H, Addonizio K, Glader B, Morton DH, Chonat S, Thompson AA, et al. The pyruvate kinase (PK) to hexokinase enzyme activity ratio and erythrocyte PK protein level in the diagnosis and phenotype of PK deficiency. Br J Haematol. 2021 Mar;192(6):1092–6.
Al-Samkari, Hanny, et al. “The pyruvate kinase (PK) to hexokinase enzyme activity ratio and erythrocyte PK protein level in the diagnosis and phenotype of PK deficiency.Br J Haematol, vol. 192, no. 6, Mar. 2021, pp. 1092–96. Pubmed, doi:10.1111/bjh.16724.
Al-Samkari H, Addonizio K, Glader B, Morton DH, Chonat S, Thompson AA, Kuo KHM, Ravindranath Y, Wang H, Rothman JA, Kwiatkowski JL, Kung C, Kosinski PA, Al-Sayegh H, London WB, Grace RF. The pyruvate kinase (PK) to hexokinase enzyme activity ratio and erythrocyte PK protein level in the diagnosis and phenotype of PK deficiency. Br J Haematol. 2021 Mar;192(6):1092–1096.
Journal cover image

Published In

Br J Haematol

DOI

EISSN

1365-2141

Publication Date

March 2021

Volume

192

Issue

6

Start / End Page

1092 / 1096

Location

England

Related Subject Headings

  • Severity of Illness Index
  • Pyruvate Metabolism, Inborn Errors
  • Pyruvate Kinase
  • Middle Aged
  • Male
  • Infant
  • Immunology
  • Humans
  • Hexokinase
  • Female