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Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency(CNSHA8)

MedGen UID:
341470
•Concept ID:
C1849507
•
Disease or Syndrome
Synonyms: CNSHA8; HEMOLYTIC ANEMIA DUE TO P5N DEFICIENCY; HEMOLYTIC ANEMIA DUE TO UMPH1 DEFICIENCY; P5N DEFICIENCY; PYRIMIDINE 5-PRIME NUCLEOTIDASE DEFICIENCY, HEMOLYTIC ANEMIA DUE TO; UMPH1 DEFICIENCY; Uridine 5-prime monophosphate hydrolase deficiency, hemolytic anemia due to
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): NT5C3A (7p14.3)
 
Monarch Initiative: MONDO:0009946
OMIM®: 266120
Orphanet: ORPHA35120

Definition

A deficiency of pyrimidine 5-prime nucleotidase (P5N), also called uridine 5-prime monophosphate hydrolase (UMPH1), causes congenital nonspherocytic hemolytic anemia-8 (CNSHA8), which is characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. The enzyme is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. Hirono et al. (1988) suggested that this deficiency is the third most common RBC enzymopathy--after G6PD (300908) and pyruvate kinase (see 266200) deficiencies--causing hemolysis (summary by Marinaki et al., 2001). [from OMIM]

Clinical features

From HPO
Hemoglobinuria
MedGen UID:
6792
•Concept ID:
C0019048
•
Finding
The presence of free hemoglobin in the urine.
See: Feature record | Search on this feature
Hemolytic anemia
MedGen UID:
1916
•Concept ID:
C0002878
•
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
See: Feature record | Search on this feature
Reticulocytosis
MedGen UID:
60089
•Concept ID:
C0206160
•
Finding
An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation.
See: Feature record | Search on this feature
Hyperbilirubinemia
MedGen UID:
86321
•Concept ID:
C0311468
•
Finding
An increased amount of bilirubin in the blood.
See: Feature record | Search on this feature
Reduced circulating pyrimidine 5-prime-nucleotidase activity
MedGen UID:
1053808
•Concept ID:
CN376753
•
Finding
The activity of concentration of pyrimidine 5-prime-nucleotidase (EC 3.1.3.5) in the blood circulation is below the lower limit of normal.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHemolytic anemia due to pyrimidine 5' nucleotidase deficiency
Follow this link to review classifications for Hemolytic anemia due to pyrimidine 5' nucleotidase deficiency in Orphanet.

Recent clinical studies

Etiology

Confounding factors in the diagnosis and clinical course of rare congenital hemolytic anemias.
Fattizzo B, Giannotta JA, Cecchi N, Barcellini W
Orphanet J Rare Dis 2021 Oct 9;16(1):415. doi: 10.1186/s13023-021-02036-4. PMID: 34627331Free PMC Article
Structure of pyrimidine 5'-nucleotidase type 1. Insight into mechanism of action and inhibition during lead poisoning.
Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr
J Biol Chem 2006 Jul 21;281(29):20521-9. Epub 2006 May 3 doi: 10.1074/jbc.M602000200. PMID: 16672222
Molecular characterization of six unrelated Italian patients affected by pyrimidine 5'-nucleotidase deficiency.
Bianchi P, Fermo E, Alfinito F, Vercellati C, Baserga M, Ferraro F, Guzzo I, Rotoli B, Zanella A
Br J Haematol 2003 Sep;122(5):847-51. doi: 10.1046/j.1365-2141.2003.04532.x. PMID: 12930399
Pyrimidine 5'-nucleotidase acquired deficiency in beta-thalassemia: involvement of enzyme-SH groups in the inactivation process.
David O, Vota MG, Piga A, Ramenghi U, Bosia A, Pescarmona GP
Acta Haematol 1989;82(2):69-74. doi: 10.1159/000205286. PMID: 2552730
Pyrimidine 5'nucleotidase and several other red cell enzyme activities in beta-thalassaemia trait.
Vives Corrons JL, Pujades MA, Aguilar i Bascompte JL, Jou JM, Rozman C, Ester A
Br J Haematol 1984 Mar;56(3):483-94. doi: 10.1111/j.1365-2141.1984.tb03978.x. PMID: 6320862

Diagnosis

Diagnosis and clinical management of enzymopathies.
Luzzatto L
Hematology Am Soc Hematol Educ Program 2021 Dec 10;2021(1):341-352. doi: 10.1182/hematology.2021000266. PMID: 34889365Free PMC Article
Confounding factors in the diagnosis and clinical course of rare congenital hemolytic anemias.
Fattizzo B, Giannotta JA, Cecchi N, Barcellini W
Orphanet J Rare Dis 2021 Oct 9;16(1):415. doi: 10.1186/s13023-021-02036-4. PMID: 34627331Free PMC Article
Proteomics reveals reduced expression of transketolase in pyrimidine 5'-nucleotidase deficient patients.
Barasa BA, van Oirschot BA, Bianchi P, van Solinge WW, Heck AJ, van Wijk R, Slijper M
Proteomics Clin Appl 2016 Aug;10(8):859-69. doi: 10.1002/prca.201500130. PMID: 27381654
The hemoglobin E thalassemias.
Fucharoen S, Weatherall DJ
Cold Spring Harb Perspect Med 2012 Aug 1;2(8) doi: 10.1101/cshperspect.a011734. PMID: 22908199Free PMC Article
Hereditary pyrimidine 5'-nucleotidase deficiency: from genetics to clinical manifestations.
Zanella A, Bianchi P, Fermo E, Valentini G
Br J Haematol 2006 Apr;133(2):113-23. doi: 10.1111/j.1365-2141.2006.05992.x. PMID: 16611302

Therapy

Splenectomy complicated by sustained extreme thrombocytosis and extensive portosplenomesenteric vein thrombosis in pyrimidine 5'-nucleotidase deficiency.
Al-Jafar HA, Taqi A, Madda JP, Abdullah TA
BMJ Case Rep 2013 Nov 28;2013 doi: 10.1136/bcr-2013-201061. PMID: 24287477Free PMC Article
Evaluation of activity of erythrocyte pyrimidine 5'-nucleotidase (P5N) in lead exposed workers: with focus on the effect on hemoglobin.
Kim Y, Yoo CI, Lee CR, Lee JH, Lee H, Kim SR, Chang SH, Lee WJ, Hwang CH, Lee YH
Ind Health 2002 Jan;40(1):23-7. doi: 10.2486/indhealth.40.23. PMID: 11926511
Erythrocyte CDP-choline accumulation in haemolytic anaemia and renal failure (RF).
Laurence A, Duley JA, Simmonds HA, Layton M, Rose SJ, Kelly SJ
Adv Exp Med Biol 1998;431:155-9. doi: 10.1007/978-1-4615-5381-6_30. PMID: 9598050
Decreased expression of CD73 (ecto-5'-nucleotidase) in the CD8+ subset is associated with zinc deficiency in human patients.
Beck FW, Kaplan J, Fine N, Handschu W, Prasad AS
J Lab Clin Med 1997 Aug;130(2):147-56. doi: 10.1016/s0022-2143(97)90091-3. PMID: 9280142
Hemolytic anemia associated with lead poisoning from shotgun pellets and the response to Succimer treatment.
Aly MH, Kim HC, Renner SW, Boyarsky A, Kosmin M, Paglia DE
Am J Hematol 1993 Dec;44(4):280-3. doi: 10.1002/ajh.2830440412. PMID: 8238001

Prognosis

Confounding factors in the diagnosis and clinical course of rare congenital hemolytic anemias.
Fattizzo B, Giannotta JA, Cecchi N, Barcellini W
Orphanet J Rare Dis 2021 Oct 9;16(1):415. doi: 10.1186/s13023-021-02036-4. PMID: 34627331Free PMC Article
Functional analysis of pyrimidine 5'-nucleotidase mutants causing nonspherocytic hemolytic anemia.
Chiarelli LR, Bianchi P, Fermo E, Galizzi A, Iadarola P, Mattevi A, Zanella A, Valentini G
Blood 2005 Apr 15;105(8):3340-5. Epub 2004 Dec 16 doi: 10.1182/blood-2004-10-3895. PMID: 15604219
Is hemoglobin instability important in the interaction between hemoglobin E and beta thalassemia?
Rees DC, Clegg JB, Weatherall DJ
Blood 1998 Sep 15;92(6):2141-6. PMID: 9731073
The hemoglobin E syndromes.
Rees DC, Styles L, Vichinsky EP, Clegg JB, Weatherall DJ
Ann N Y Acad Sci 1998 Jun 30;850:334-43. doi: 10.1111/j.1749-6632.1998.tb10490.x. PMID: 9668555

Clinical prediction guides

A rare mutation (p.F149del) of the NT5C3A gene is associated with pyrimidine 5'-nucleotidase deficiency.
Bogusławska DM, Skulski M, Bartoszewski R, Machnicka B, Heger E, Kuliczkowski K, Sikorski AF
Cell Mol Biol Lett 2022 Nov 24;27(1):104. doi: 10.1186/s11658-022-00405-w. PMID: 36434495Free PMC Article
Molecular characterization of six unrelated Italian patients affected by pyrimidine 5'-nucleotidase deficiency.
Bianchi P, Fermo E, Alfinito F, Vercellati C, Baserga M, Ferraro F, Guzzo I, Rotoli B, Zanella A
Br J Haematol 2003 Sep;122(5):847-51. doi: 10.1046/j.1365-2141.2003.04532.x. PMID: 12930399
Chronic non-spherocytic haemolytic anaemia due to congenital pyrimidine 5' nucleotidase deficiency: 25 years later.
Vives i Corrons JL
Baillieres Best Pract Res Clin Haematol 2000 Mar;13(1):103-18. doi: 10.1053/beha.1999.0060. PMID: 10916681
Enhanced activity of pyrimidine 5'-nucleotidase in rat red blood cells during erythropoiesis.
Hokari S, Miyazaki T, Hasegawa M, Komoda T
Biol Chem 1998 Mar;379(3):329-33. doi: 10.1515/bchm.1998.379.3.329. PMID: 9563829
Pyrimidine 5'nucleotidase and several other red cell enzyme activities in beta-thalassaemia trait.
Vives Corrons JL, Pujades MA, Aguilar i Bascompte JL, Jou JM, Rozman C, Ester A
Br J Haematol 1984 Mar;56(3):483-94. doi: 10.1111/j.1365-2141.1984.tb03978.x. PMID: 6320862

Supplemental Content

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    Clinical resources

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    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • MeSH
      Related Medical Subject Headings
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
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