Uridine monophosphate hydrolase deficiency

MedGen UID:: 574095
•Concept ID:: C0340969
•: Disease or Syndrome

Synonyms:	Pyrimidine-5'-Nucleotidase Deficiency; Pyrimidine-5-nucleotidase deficiency
SNOMED CT:	Uridine monophosphate hydrolase deficiency (234407001); Pyrimidine-5-nucleotidase deficiency (234407001)

Definition

An autosomal recessive disorder caused by mutation of the NT5C3A gene. It is the most frequent abnormality of red cell nucleotide metabolism, causing chronic, non-spherocytic hemolytic anemia. Most affected individuals have Mediterranean, Jewish, or African ancestry. Basophilic stippling and accumulation of pyrimidines within erythrocytes are hallmarks of this disorder. [from NCI]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVUridine monophosphate hydrolase deficiency

Phenotypic abnormality
- Abnormality of blood and blood-forming tissues
  - Abnormal erythrocyte morphology
    - Anemia
      - Anemia due to disorders of nucleotide metabolism
        Uridine monophosphate hydrolase deficiency

Recent clinical studies

Etiology

The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.

Ali RA, Awadalla EA, Amin YA, Fouad SS, Ahmed MAB, Hassan MH, Abdel-Kahaar E, Abdel-Aziz RH
Sci Rep 2024 Mar 7;14(1):5682. doi: 10.1038/s41598-024-55950-5. PMID: 38453980 Free PMC Article

A new simple approach for the determination of pyrimidine 5'-nucleotidase activity in human erythrocytes using an ELISA reader.

Warang P, Kedar P, Ghosh K, Colah R
Int J Lab Hematol 2012 Jun;34(3):232-6. Epub 2011 Nov 14 doi: 10.1111/j.1751-553X.2011.01381.x. PMID: 22078096

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Diagnosis

A New Homozygous Mutation (c.393-394del TA/c.393-394del TA) in the NT5C3 Gene Associated With Pyrimidine-5'-Nucleotidase Deficiency: A Case Report.

Köker SA, Oymak Y, Bianchi P, Fermo E, Karapinar TH, Gözmen S, Ay Y, Vergin RC
J Pediatr Hematol Oncol 2019 Nov;41(8):e484-e486. doi: 10.1097/MPH.0000000000001482. PMID: 30951028

Diagnosis of pyrimidine 5'-nucleotidase deficiency suspected from a blood film.

Al-Jafar HA, Layton DM, Robertson L, Escuredo E, Bain BJ
Am J Hematol 2013 Dec;88(12):1089. Epub 2013 Aug 30 doi: 10.1002/ajh.23556. PMID: 23897698

Molecular basis of pyrimidine 5'-nucleotidase deficiency caused by 3 newly identified missense mutations (c.187T>C, c.469G>C and c.740T>C) and a tabulation of known mutations.

Chiarelli LR, Morera SM, Galizzi A, Fermo E, Zanella A, Valentini G
Blood Cells Mol Dis 2008 May-Jun;40(3):295-301. doi: 10.1016/j.bcmd.2007.10.005. PMID: 18499901

Identification of thymidine nucleotidase and deoxyribonucleotidase activities among normal isozymes of 5'-nucleotidase in human erythrocytes.

Paglia DE, Valentine WN, Brockway RA
Proc Natl Acad Sci U S A 1984 Jan;81(2):588-92. doi: 10.1073/pnas.81.2.588. PMID: 6320196 Free PMC Article

A radioassay for pyrimidine-5'-nucleotidase activity.

Buc H, Kaplan JC
Clin Chim Acta 1978 Apr 17;85(2):193-6. doi: 10.1016/0009-8981(78)90239-5. PMID: 647979

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Therapy

Ali RA, Awadalla EA, Amin YA, Fouad SS, Ahmed MAB, Hassan MH, Abdel-Kahaar E, Abdel-Aziz RH
Sci Rep 2024 Mar 7;14(1):5682. doi: 10.1038/s41598-024-55950-5. PMID: 38453980 Free PMC Article

Low-density lipoprotein receptor-deficient hepatocytes differentiated from induced pluripotent stem cells allow familial hypercholesterolemia modeling, CRISPR/Cas-mediated genetic correction, and productive hepatitis C virus infection.

Caron J, Pène V, Tolosa L, Villaret M, Luce E, Fourrier A, Heslan JM, Saheb S, Bruckert E, Gómez-Lechón MJ, Nguyen TH, Rosenberg AR, Weber A, Dubart-Kupperschmitt A
Stem Cell Res Ther 2019 Jul 29;10(1):221. doi: 10.1186/s13287-019-1342-6. PMID: 31358055 Free PMC Article

Successful Treatment With Ledipasvir/Sofosbuvir in an Infant With Severe Combined Immunodeficiency Caused by Adenosine Deaminase Deficiency With HCV Allowed Gene Therapy with Strimvelis.

Tucci F, Calbi V, Barzaghi F, Migliavacca M, Ferrua F, Bernardo ME, Canarutto D, Consiglieri G, Recupero S, Calzatini F, Gabaldo M, Lucano C, Casiraghi M, Darin S, Dionisio F, Marktel S, Cestone E, Finazzi R, Mieli-Vergani G, Boeri E, Appleby J, Abd Elaziz D, Ciceri F, Aiuti A, Cicalese MP
Hepatology 2018 Dec;68(6):2434-2437. Epub 2018 Nov 13 doi: 10.1002/hep.30160. PMID: 30014500 Free PMC Article

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: 24287477 Free PMC Article

Use of 5-fluorodeoxycytidine and tetrahydrouridine to exploit high levels of deoxycytidylate deaminase in tumors to achieve DNA- and target-directed therapies.

Mekras JA, Boothman DA, Perez LM, Greer S
Cancer Res 1984 Jun;44(6):2551-60. PMID: 6539164

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Prognosis

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

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Clinical prediction guides

Contribution of Cytidine Deaminase to Thymidylate Biosynthesis in Trypanosoma brucei: Intracellular Localization and Properties of the Enzyme.

Moro-Bulnes A, Castillo-Acosta VM, Valente M, Carrero-Lérida J, Pérez-Moreno G, Ruiz-Pérez LM, González-Pacanowska D
mSphere 2019 Aug 7;4(4) doi: 10.1128/mSphere.00374-19. PMID: 31391279 Free PMC Article

Identification of thymidine nucleotidase and deoxyribonucleotidase activities among normal isozymes of 5'-nucleotidase in human erythrocytes.

Paglia DE, Valentine WN, Brockway RA
Proc Natl Acad Sci U S A 1984 Jan;81(2):588-92. doi: 10.1073/pnas.81.2.588. PMID: 6320196 Free PMC Article

Analysis of human erythrocyte 5'-nucleotidases in healthy individuals and a patient deficient in pyrimidine 5'-nucleotidase.

Swallow DM, Aziz I, Hopkinson DA, Miwa S
Ann Hum Genet 1983 Jan;47(1):19-23. doi: 10.1111/j.1469-1809.1983.tb00966.x. PMID: 6301356

Pyrimidine metabolism in erythrocytes of the newborn.

Tax WJ, Veerkamp JH, Schretlen ED
Biol Neonate 1979;35(3-4):121-5. doi: 10.1159/000241162. PMID: 435586

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