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.

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

Patients older than 5 years and younger than 30 years old, with high suspicion of PK deficiency, due to chronic anaemia or cholelithiasis or cholecystitis of undetermined aetiology

The plan will be defined at a later stages