Pyruvate Kinase Deficiency Epidemiological Study (PIECE)

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.

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Key information

Conditions

Pyruvate Kinase Deficiency Pyruvate Kinase Deficiency of Red Cells

Age range

5 year–30 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Intervent Clinical Research Center

Pembroke Pines, Florida, 33024, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

Identification of 100 PKLR positive participants out of a cohort of 16,000 PK deficiency-suspected cases

Time frame: 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 outcomes

Biomarker/s establishment in PKLR-positive cohort

Time frame: 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.

Sponsors and collaborators

Lead sponsor

CENTOGENE GmbH Rostock

Industry

Registry information

Official study title

Pyruvate Kinase Deficiency Epidemiological Study. An International, Multicentre, Epidemiological Observational Study

Acronym: PIECE

Important dates

Study start: 2020
Primary completion: 2021
Study completion: 2021
First posted: Mar 7, 2019
Registry last updated: Feb 9, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed