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Hereditary pyrimidine 5′‐nucleotidase deficiency: from genetics to clinical manifestations
Author(s) -
Zanella Alberto,
Bianchi Paola,
Fermo Elisa,
Valentini Giovanna
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.05992.x
Subject(s) - biology , 5' nucleotidase , nucleotidase , gene , nucleotide , mutation , enzyme , genetics , microbiology and biotechnology , biochemistry
Summary Hereditary pyrimidine 5′‐nucleotidase (P5′N) deficiency is the most frequent abnormality of the red cell nucleotide metabolism causing hereditary non‐spherocytic haemolytic anaemia. The disorder is usually characterised by mild‐to‐moderate haemolytic anaemia associated with the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. The precise mechanisms leading to the destruction of P5′N deficient red cells are still unclear. The pyrimidine 5′‐nucleotidase type‐I (P5′N‐1) gene is localised on 7p15‐p14 and the cDNA has been cloned and sequenced; 20 mutations have been identified so far in 30 unrelated families, most of them at the homozygous level. Recently, the comparison of recombinant mutants of human P5′N‐1 with the wild‐type enzyme has enabled the effects of amino acid replacements on the enzyme molecular properties to be determined and help to correlate genotype to clinical phenotype.