Hereditary erythrocyte pyrimidine 5'-nucleotidase deficiency: a biochemical, genetic and clinical overview

Pyrimidine 5' -nucleotidase (P5'N-1) deficiency is the third most common enzyme abnormality after glucose 6-phosphate dehydrogenase and pyruvate kinase causing hereditary non-spherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait. The degree of hemolysis is generally mild-to moderate. The hallmark of this enzyme deficiency is the presence of pronounced basophylic stippling in red blood cell peripheral blood smear together with accumulation of pyrimidine nucleotides within erythrocytes. No correlation has been found between residual activity and degree of hemolysis. The structural human gene for P5'N-1 is now available and fifteen different mutations had been identified so far. More recently, a functional analysis of P5'N-1 mutants had been performed providing a rationale for the pathological effects of the mutations. All mutations investigated affect amino acid residues unambiguously essential for the catalytic efficiency and/or protein stability, suggesting drastic reduction of the enzyme activity in red blood cells of patients affected by the disorder. Nevertheless, some patients exhibit high residual P5'N-1 activity, suggesting that P5'N-1 deficiency is compensate by other nucleotidases and/or alternative pathways in nucleotide metabolism. No specific therapy for P5'N-1 deficiency is now available