Contributions
Abstract: EP699
Type: E-Poster Presentation
Session title: Enzymopathies, membranopathies and other anemias
Background
Non-spherocytic hemolytic anemia due to erythrocyte pyruvate kinase deficiency (PKD) is an autosomal recessive disorder associated with more than three hundred mutations in PKLR gene. PKD characterized by anemia, jaundice, and splenomegaly.
Until now we have no data on the incidence and prevalence of this disease in Russia. Due to the technical difficulties of conducting a study of erythrocyte pyruvate kinase activity, genetic research is currently the main method for diagnosing this disease in Russia.
Aims
The aim of our study was to create an overview of the PKD population in the Russian Federation.
Methods
We performed a retrospective analysis of data from 43 genetically confirmed cases of PKD. All patients had undergone at least one assessment at our center. The diagnosis was confirmed by next generation sequencing using the Hemolytic Anemia Panel, a 75-gene panel for inherited anemias. Clinical and genetic characteristics were collected from patient records.
Results
Forty-three patients were enrolled. The median age is 5 years old (4 month – 26 years old). The age at diagnosis varied between 4 month and 26 years. The ratio male : female was 1:1.53. At least once transfusion of erythrocyte suspension was required to 42 (97.67%) patients. The minimum age at the debut of transfusion dependence was the first day of life, the maximum – 4 years. Exchange blood transfusion was performed for 14 children, transfusion of packed red blood cells during the first year of life was noted for 40 children; 2 children underwent single transfusions on the background of infectious episodes at 3 and 4 years respectively. Clinically, 43 patients (100%) had an anemia, 29/37 (78,38%) had a splenomegaly and 132 (74,42%) had a jaundice. Iron overload, requiring the chelation therapy, was found in 11 (25.58%) patients. Splenectomy due to high transfusion dependence was performed in 10 patients: transfusion independence was achieved in 5 of them, for the rest cases – an increase of the interval between blood transfusions. Median of surgical intervention is 7 years 4 months, (min – max 1 year 4 months – 14 years 4 months).
The homozygous mutations in the PKLR gene were found in 11 patients (25.58%), compound heterozygous mutations in 32 patients (74.42%), 78.67% of them were missense mutations. 36 genotypes were described in 43 patients, among them were: c.1529G>A/c.1529G>A (n=4), c.1137_1139del/c.1456C>T (n=2), c.1079G>A/c.1529G> A (n=2), c.1130T>C/c.1456C>T (n=2), c. c.1174G>A/c.1456C> T (n=2), other genotypes occurred once. Two mutations were the most frequent: c.1529G>A (17.33%) and c.1456C>T (17.33%). Previously not described mutations were identified for 19 (44.19%) patients.
Conclusion
Patients with PKD are characterized by a predominance of severe course of the disease with early onset and transfusion dependence. PKD is rare for our country with a total number of 43 pediatric patients (2013-2021). The observed clinical and genetic heterogeneity in our cohort highlights the need for interdisciplinary approach and further studies.
Keyword(s): Anemia, Erythrocyte, Genetic
Abstract: EP699
Type: E-Poster Presentation
Session title: Enzymopathies, membranopathies and other anemias
Background
Non-spherocytic hemolytic anemia due to erythrocyte pyruvate kinase deficiency (PKD) is an autosomal recessive disorder associated with more than three hundred mutations in PKLR gene. PKD characterized by anemia, jaundice, and splenomegaly.
Until now we have no data on the incidence and prevalence of this disease in Russia. Due to the technical difficulties of conducting a study of erythrocyte pyruvate kinase activity, genetic research is currently the main method for diagnosing this disease in Russia.
Aims
The aim of our study was to create an overview of the PKD population in the Russian Federation.
Methods
We performed a retrospective analysis of data from 43 genetically confirmed cases of PKD. All patients had undergone at least one assessment at our center. The diagnosis was confirmed by next generation sequencing using the Hemolytic Anemia Panel, a 75-gene panel for inherited anemias. Clinical and genetic characteristics were collected from patient records.
Results
Forty-three patients were enrolled. The median age is 5 years old (4 month – 26 years old). The age at diagnosis varied between 4 month and 26 years. The ratio male : female was 1:1.53. At least once transfusion of erythrocyte suspension was required to 42 (97.67%) patients. The minimum age at the debut of transfusion dependence was the first day of life, the maximum – 4 years. Exchange blood transfusion was performed for 14 children, transfusion of packed red blood cells during the first year of life was noted for 40 children; 2 children underwent single transfusions on the background of infectious episodes at 3 and 4 years respectively. Clinically, 43 patients (100%) had an anemia, 29/37 (78,38%) had a splenomegaly and 132 (74,42%) had a jaundice. Iron overload, requiring the chelation therapy, was found in 11 (25.58%) patients. Splenectomy due to high transfusion dependence was performed in 10 patients: transfusion independence was achieved in 5 of them, for the rest cases – an increase of the interval between blood transfusions. Median of surgical intervention is 7 years 4 months, (min – max 1 year 4 months – 14 years 4 months).
The homozygous mutations in the PKLR gene were found in 11 patients (25.58%), compound heterozygous mutations in 32 patients (74.42%), 78.67% of them were missense mutations. 36 genotypes were described in 43 patients, among them were: c.1529G>A/c.1529G>A (n=4), c.1137_1139del/c.1456C>T (n=2), c.1079G>A/c.1529G> A (n=2), c.1130T>C/c.1456C>T (n=2), c. c.1174G>A/c.1456C> T (n=2), other genotypes occurred once. Two mutations were the most frequent: c.1529G>A (17.33%) and c.1456C>T (17.33%). Previously not described mutations were identified for 19 (44.19%) patients.
Conclusion
Patients with PKD are characterized by a predominance of severe course of the disease with early onset and transfusion dependence. PKD is rare for our country with a total number of 43 pediatric patients (2013-2021). The observed clinical and genetic heterogeneity in our cohort highlights the need for interdisciplinary approach and further studies.
Keyword(s): Anemia, Erythrocyte, Genetic