Pyruvate Kinase Deficiency
Conditions
Keywords
Pyruvate Kinase Deficiency, Chronic anaemia, Biomarker
Brief summary
Pyruvate kinase deficiency (PKD) is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia, caused by mutations in the PKLR gene. The main goal of this study is the diagnosis of pyruvate kinase deficiency in patients who exhibit chronic anaemia and/or splenomegaly and/or judiance and/or hyperbilirubinemia and/or history of prolonged neonatal jaundice and/ or cholelithiasis of undetermined aetiology.
Detailed description
Pyruvate kinase deficiency is the most common red cell glycolytic enzyme defect causing hereditary non-spherocytic hemolytic anemia, caused by mutations in the PKLR gene. PKLR encodes a pyruvate kinase that catalyzes the transphosphorylation of phosphoenolpyruvate into pyruvate and ATP. The current treatment options are red cell transfusions, chelation and splenectomy. This is an international, multicentre, epidemiological and observational study. The patients fulfilling the inclusion criteria will be enrolled into the Study and genetically tested for PKLR mutations via Next generation sequencing (NGS). Any mutation being detected by NGS, will be confirmed by Sanger sequencing. PKLR-positive samples (homozygous or compound heterozygous for pathogenic variants) will be analysed for the identification of potential biomarkers via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared to a merged control samples in order establish a PKD specific biomarker.
Interventions
None listed
Sponsors
CENTOGENE GmbH Rostock
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
5 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent is obtained from the participant or legal representative * The participant is equal or older than 5 years or equal or younger than 30 years old * The participant exhibits the following symptoms of no obvious etiology: * chronic anaemia and/or * splenomegaly and/or * jaundice and/or * cholelithiasis and/or * cholecystitis and/or * hyperbilirubinemia and/or * history of prolonged neonatal jaundice * The participant is clinically diagnosed with PK deficiency
Exclusion criteria
* Inability to provide informed consent * The participant does not suffer from chronic anaemia and splenomegaly and jaundice and cholelithiasis and cholecystitis and hyperbilirubinemia and history of prolonged neonatal jaundice * The etiology of chronic anaemia or splenomegaly or jaundice or cholelithiasis or cholecystitis or kernicterus is clearly determined and is not due to PK deficiency * The participant is younger than 5 years or older than 30 years old * Previously enrolled in the PIECE Study * Participant in custody
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of 100 PKLR positive participants out of a cohort of 16,000 PK deficiency-suspected cases | 24 months | Number of identified pyruvate kinase deficiency patients, which showing a mutation/pathogenic variant in their PKLR gene, within a cohort of 16.000 suspected cases via using respective patients' dry blood sample for confirmatory testing (next generation sequencing of PKLR gene) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarker/s establishment in PKLR-positive cohort | 24 months | The quantitative determination of small molecules within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry, and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker. |
Countries
United States
Outcome results
None listed