Acquired Red Cell Pyruvate Kinase Deficiency
in Leukemias and Related Disorders

Pyruvate kinase (PK) deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia. The prevalence of this deficiency is unknown, though some estimates have been made based on the frequency of low red cell PK activity in the population. An additional 20 patients with hereditary nonspherocytic hemolytic anemia caused by PK deficiency have been genotyped. One previously unreported mutation 1153C→T (R385W) was encountered. The relative frequency of PK mutations in patients with hemolytic anemia caused by PK deficiency was calculated from the 18 white patients reported here and from 102 patients previously reported in the literature. DNA samples from 3785 subjects from different ethnic groups have been screened for the 4 more frequently encountered mutations—c.1456 C→T(1456T), c.1468 C→T(1468T), c.1484 C→T(1484T), and c.1529 G6A (1529A)—by allele-specific oligonucleotide hybridization. Among white patients the frequency of the 1456T mutation was 3.50 × 10−3; that of the 1529A mutation was 2.03 × 10−3. Among African Americans the frequency of the 1456T mutation was 3.90 × 10−3 The only mutation found in the limited number of Asians tested was 1468T at a frequency of 7.94 × 10−3. Based on the gene frequency of the 1529A mutation in the white population and on its relative abundance in patients with hemolytic anemia caused by PK deficiency, the prevalence of PK deficiency is estimated at 51 cases per million white population. This number would be increased by inbreeding and decreased by failure of patients with PK deficiency to survive.

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Comments on an optimized assay for red cell pyruvate kinase deficiency

Clinica Chimica Acta ◽

10.1016/0009-8981(81)90059-0 ◽

1981 ◽

Vol 116 (3) ◽

pp. 397-399

Author(s):

Ernest Beutler

Keyword(s):

Pyruvate Kinase ◽

Red Cell ◽

Pyruvate Kinase Deficiency

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Red Cell Pyruvate Kinase Deficiency: Adverse Effect of Oral Contraceptives

Acta Haematologica ◽

10.1159/000207868 ◽

1977 ◽

Vol 57 (2) ◽

pp. 116-120 ◽

Cited By ~ 5

Author(s):

Alan G. Kendall ◽

Gloria F. Charlow

Keyword(s):

Adverse Effect ◽

Pyruvate Kinase ◽

Oral Contraceptives ◽

Red Cell ◽

Pyruvate Kinase Deficiency

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Pyruvate kinase deficiency: epidemiology, molecular analyses and modern diagnostic approaches (literature review)

Russian Journal of Pediatric Hematology and Oncology ◽

10.21682/2311-1267-2020-7-2-86-93 ◽

2020 ◽

Vol 7 (2) ◽

pp. 86-93

Author(s):

A. V. Bankole ◽

E. A. Chernyak

Keyword(s):

Pyruvate Kinase ◽

Hemolytic Anemia ◽

Molecular Genetic ◽

Clinical Manifestations ◽

Diagnostic Methods ◽

Compound Heterozygous ◽

Red Cell ◽

Molecular Genetic Study ◽

Pyruvate Kinase Deficiency ◽

Diagnostic Approaches

Red cell pyruvate kinase deficiency is the most common glycolytic defect causing congenital nonspherocytic hemolytic anemia. Pyruvate kinase is the enzyme involved in the last step of glycolysis – the transfer of a phosphate group from phosphoenolpyruvate producing the enolate of pyruvate and ATP (50 % of total energy ATP of erythrocytes). ATP deficiency directly shortened red cell lifespan. Affected red blood cells are destroyed in the splenic capillaries, leading to the development of chronic hemolytic anemia. It is an autosomal recessive disease, caused by homozygous and compound heterozygous mutations in the PKLR gene. There are no exact data on the incidence of pyruvate kinase deficiency, but the estimated frequency varies from 3: 1,000,000 to 1:20,000. The clinical features of the disease and the severity are highly variable. Diagnosis of pyruvate kinase deficiency is based on the determination of pyruvate kinase activity and molecular genetic study of the PKLR gene. The variety of clinical manifestations, possible complications, as well as the inaccessibility of diagnostic methods complicate the diagnosis.

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