Severe hemolytic anemia in a Vietnamese family, associated with novel mutations in the gene encoding for pyruvate kinase | Haematologica

摘要

BACKGROUND AND OBJECTIVES: Chronic hemolytic anemias are very frequent diseases in intertropical countries mainly caused by hemoglobin disorders. We studied a Vietnamese family in which a first child suffered from a severe transfusion-dependent anemia. The family requested an antenatal diagnosis during a second pregnancy. To characterize the molecular defect, we studied the family over three generations. DESIGN AND METHODS: Blood from family members was sampled for a full hematologic evaluation, including enzymatic dosage, and DNA analysis was performed for patients displaying pyruvate kinase deficiency (PK-R). Mutation research on the 11 exons of the PKLR gene was done using a scanning method and sequencing. Deletion was evidenced by a Sybergreen based quantitative real time polymerase chain reaction (PCR) and mapped using quantitative multiplex PCR of short fluorescent fragments spread along the whole sequence of the PKLR gene. RESULTS: Hematologic and molecular studies of this severe chronic anemia demonstrated the existence of two defects in the PKLR gene, a new mutation located on exon 7: c.948C->G (N316K) and a large deletion extending from exon 4 to exon 10. INTERPRETATION AND CONCLUSIONS: We describe a family in a south-east Asian country; the proband had severe transfusion-dependent chronic anemia caused by the association between two PKLR gene mutations, PK Saigon (N316K) and PK Viet del 4-10. Severe chronic anemia could be induced by various molecular defects mainly affecting the globin genes. However, even in populations in which hemoglobin diseases are frequent, enzymatic diseases should be considered.