Adenosine Triphosphate, Elevated, Of Erythrocytes

A number sign (#) is used with this entry because of evidence that the phenotype of hereditary increase of red blood cell ATP is caused by heterozygous mutation in the PKLR (609712) on chromosome 1q22.

Clinical Features

Brewer (1965) in the United States and Zurcher et al. (1965) in Holland described high erythrocyte adenosine triphosphate as a dominantly inherited trait. 'High red cell ATP syndrome' may be a heterogeneous category. For example, pyrimidine-5-prime-nucleotidase deficiency (266120) hemolytic anemia shows this feature. Max-Audit et al. (1980) described a family in which 4 persons had polycythemia and pyruvate kinase hyperactivity. They showed low 2,3-diphosphoglycerate (2,3-DPG) and high adenosine triphosphate (ATP) levels. The PK electrophoretic patterns in these persons were abnormal by the presence of several additional bands.

Molecular Genetics

Beutler et al. (1997) restudied the family described by Zurcher et al. (1965) and by SSCP analysis found a band shift in exon 2 of the red cell pyruvate kinase gene resulting from a point mutation at nucleotide 110. Beutler (1997) verified the mutation as a G-to-A transition resulting in a gly37-to-glu amino acid substitution (609712.0008). The mutation was present in heterozygous state. Beutler et al. (1997) stated it is possible that different mutations in the PKLR gene are responsible for the finding in other families with elevated red cell ATP levels, because the enzyme kinetics in other families have been different from those in the family reported by Zurcher et al. (1965).