This cross-sectional prevalence assessment study involves a single blood draw in specific patient populations to assess for enzymatic and genomic evidence for acquired pyruvate kinase deficiency.
This cross-sectional prevalence assessment study involves a single blood draw in specific patient populations to assess for enzymatic and genomic evidence for acquired pyruvate kinase deficiency. * Red cell pyruvate kinase enzyme activity and next-generation sequencing (NGS) hereditary hemolytic anemia panels will be performed on samples from all recruited participants. * The study will recruit patients to two separate cohorts. * Cohort 1 will recruit approximately 75 anemic (Hgb \<11.0 g/dL) MDS participants without overt clinical evidence of hemolysis. * Cohort 2 will recruit approximately 25 participants with clonal myeloid disorders of any type with evidence of non-immune, otherwise unexplained hemolytic anemia * Participation in the study involves a single blood draw. Basic information about the participant's blood disorder will also be collected. It is expected that about 100 people will take part in this research study
Study Type
OBSERVATIONAL
Enrollment
100
Blood specimen 2-4 teaspoons
Massachusetts General Hospital
Boston, Massachusetts, United States
Overall prevalence of possible or likely acquired pyruvate kinase deficiency
defined by PK enzyme activity or PK:HK ratio \>1 SD below the control mean (healthy subject mean) as measured by enzyme assay, or potentially pathogenic mutations in the PKLR gene as found on PKLR sequencing
Time frame: Day 1
Overall prevalence of definite acquired pyruvate kinase deficiency
Defined by PK enzyme activity below normal (or a PK:HK ratio \<8.7) as measured by enzyme assay, or known pathogenic mutations in the PKLR gene as found on PKLR sequencing
Time frame: Day 1
Red cell pyruvate kinase enzyme activity
Red cell pyruvate kinase enzyme activity in patients not receiving red cell transfusion in the 60 days prior to blood draw
Time frame: 60 days
Red cell pyruvate kinase
hexokinase enzyme activity ratio in patients not receiving red cell transfusion in the 60 days prior to blood draw
Time frame: 60 Day
Somatic mutations in PKLR (and other genes associated with acquired PKD) detected in the hematopoietic clone
Time frame: Day 1
Somatic mutations in other genes associated with hemolytic anemia detected in the hematopoietic clone
Time frame: Day 1
Characterization of pyruvate kinase-related red cell metabolites (ATP, 2,3-DPG) and pyruvate kinase-R protein in patients with clonal myeloid disorders
Time frame: Day 1
Impact of pyruvate kinase activators on PK activity in vitro
Time frame: Day 1
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