Pyruvate Kinase Deficiency Epidemiological Study (PIECE)

Completed

• Conditions: Pyruvate Kinase Deficiency

• Registration Number: NCT03866590
• Lead Sponsor: CENTOGENE GmbH Rostock

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.

Study Timeline

• Study First Submitted: 2019-03-01
• Study First Submitted QC: 2019-03-06
• Study First Posted: 2019-03-07
• Study Start: 2020-01-13
• Primary Completion: 2021-05-31
• Study Completion: 2021-05-31
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-08
• Last Update Posted: 2023-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Intervent Clinical Research Center; 🇺🇸 Pembroke Pines, Florida, United States