Chronic non-spherocytic haemolytic anaemia due to congenital pyrimidine 5′ nucleotidase deficiency: 25 years later

Functional analysis of pyrimidine 5′-nucleotidase mutants causing nonspherocytic hemolytic anemia

“…15,16 P5ЈN-1 deficiency is associated to mild to moderate anemia and, in a few cases, learning difficulties. 9,17 The diagnosis of P5ЈN-1 deficiency relies on the reduced specific activity of P5ЈN-1 and the increased concentrations of pyrimidine nucleotides in the erythrocyte. 2 In this study, we have performed a thorough biochemical and molecular analysis of P5ЈN-1 to provide the basis to establish a correlation between genotype and phenotype.…”

“…7 P5ЈN-1 deficiency is an autosomal recessive disorder characterized by hemolytic nonspherocytic anemia, heavy basophilic stippling in RBC peripheral blood smears, and accumulation of pyrimidine nucleotides within erythrocytes. 5,8,9 It has been suggested that P5ЈN-1 deficiency is the third most common RBC enzymopathy-after glucose-6-phosphate dehydrogenase and pyruvate kinase deficiency 10 -that causes hemolysis. P5ЈN-1 deficiency can also be acquired as a result of lead poisoning or oxidative threat.…”

“…P5ЈN-1 deficiency can also be acquired as a result of lead poisoning or oxidative threat. 2,9 Fourteen different mutations have been identified at the DNA level to date 7 ; 4 of them are missense mutations and do not affect the protein length, and the remaining 10 (nonsense mutations, deletions, insertions, and alterations of the splicing sites) are expected to generate shorter or aberrant forms of the polypeptide. P5ЈN-1 deficiency is generally associated with mild to moderate hemolytic anemia, 7,11 although at present no correlation between the residual P5ЈN-1 activity and the severity of clinical manifestations has been documented.…”

Lead Poisoning Induced Severe Hemolytic Anemia, Basophilic Stippling, Mimicking Erythrocyte Pyrimidine 5'-nucleotidase Deficiency in Beta Thalassemia Minor

“…There was a slight reduction in the Purine/Pyrimidine nucleotides ratio, but the activity of P5"N-1 in one case was normal. This is due to the high reticulocyte count (6.5%) or because P5'-1 activity is progressively inhibited until the erythrocyte lead concentration reaches 200 μg/dl RBC at which point the activity was maximally depressed [11]. Both the patients had no history of taking any ayurvedic or traditional medicine for their high level of lead content.…”

“…Basophilic stippling is a constant but not specific finding in this disease, occasionally occurring in other congenital or acquired conditions, such as β-thalassemia trait, some hemoglobin variants, sideroblastic anemia or pyrimidine 5'nucleotidase deficiency [8][9][10]. The lead poisoning diagnosis ultimately depends upon the high level of lead content in blood and high concentrations of pyrimidine nucleotides and a reduced P5'N-1 activity in red blood cells [11]. The nucleotides of normal red cells consist largely of purine derivatives (which have an absorption maximum at about 260 nm), with very low levels of pyrimidine nucleotides (absorption at 280 nm).…”