Pyruvate Kinase Deficiency Epidemiological Study (PIECE)

CENTOGENE GmbH Rostock75 enrolled

Overview

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.

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 Type

OBSERVATIONAL

Enrollment

Conditions

Pyruvate Kinase Deficiency

Eligibility

Sex: ALLMin age: 5 YearsMax age: 30 Years

Medical Language ↔ Plain English

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

Locations (1)

Intervent Clinical Research Center

Pembroke Pines, Florida, United States

Outcomes

Primary Outcomes

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

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)

Time frame: 24 months

Secondary Outcomes

Biomarker/s establishment in PKLR-positive cohort

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.

Time frame: 24 months

Data from ClinicalTrials.gov

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