Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation
Hereditary orotic aciduria (HOA) is a very rare inborn error of pyrimidine metabolism. It results from a defect of the uridine-5-monophosphate synthase (UMPS) gene. To date, only about twenty patients have been described. We report a case of HOA with a novel variant in the UMPS gene. A 17-year-old E...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-03-01
|
| Series: | Molecular Genetics and Metabolism Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221442692030149X |
| _version_ | 1819176212457586688 |
|---|---|
| author | Hebah S. Al Absi Stephanie Sacharow Naser Al Zein Aisha Al Shamsi Amal Al Teneiji |
| author_facet | Hebah S. Al Absi Stephanie Sacharow Naser Al Zein Aisha Al Shamsi Amal Al Teneiji |
| author_sort | Hebah S. Al Absi |
| collection | DOAJ |
| description | Hereditary orotic aciduria (HOA) is a very rare inborn error of pyrimidine metabolism. It results from a defect of the uridine-5-monophosphate synthase (UMPS) gene. To date, only about twenty patients have been described. We report a case of HOA with a novel variant in the UMPS gene. A 17-year-old Emirati girl was born to first-cousin parents. During the first year, she had recurrent, severe infections including disseminated varicella. After evaluation for immunodeficiency, an impression of immunodeficiency of unknown etiology was presumed. Frequent episodes of pancytopenia were also noted. Bone marrow biopsy showed trilineage megaloblastoid maturation with dysplastic changes that were refractory to hematinic therapy. Also, she was noted to have failure to thrive, developmental delay and epilepsy. She was referred to the Genetics clinic where whole-exome sequencing (WES) was done and showed a novel homozygous variant in the UMPS gene confirming a diagnosis of HOA. She was started on uridine triacetate after which she showed clinical, hematologic and biochemical improvement. Although extremely rare, hereditary orotic aciduria should be suspected in any child with megaloblastic bone marrow, immunodeficiency or when developmental delay and anemia coexist. |
| first_indexed | 2024-12-22T21:07:10Z |
| format | Article |
| id | doaj.art-1856f6c60f1c466c94c80f4e1a89bed8 |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-12-22T21:07:10Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-1856f6c60f1c466c94c80f4e1a89bed82022-12-21T18:12:38ZengElsevierMolecular Genetics and Metabolism Reports2214-42692021-03-0126100703Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutationHebah S. Al Absi0Stephanie Sacharow1Naser Al Zein2Aisha Al Shamsi3Amal Al Teneiji4Department of Pediatrics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab EmiratesDivision of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USADepartment of Pediatrics, Division of Hematology and Oncology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab EmiratesDepartment of Pediatrics, Division of Genetics and Metabolic, Tawam Hospital, Al Ain, United Arab EmiratesDepartment of Pediatrics, Division of Metabolic Genetics, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; Corresponding author at: Department of Pediatrics, Division of Metabolic Genetics, Sheikh Khalifa Medical City, Al Karamah St, Abu Dhabi, United Arab Emirates.Hereditary orotic aciduria (HOA) is a very rare inborn error of pyrimidine metabolism. It results from a defect of the uridine-5-monophosphate synthase (UMPS) gene. To date, only about twenty patients have been described. We report a case of HOA with a novel variant in the UMPS gene. A 17-year-old Emirati girl was born to first-cousin parents. During the first year, she had recurrent, severe infections including disseminated varicella. After evaluation for immunodeficiency, an impression of immunodeficiency of unknown etiology was presumed. Frequent episodes of pancytopenia were also noted. Bone marrow biopsy showed trilineage megaloblastoid maturation with dysplastic changes that were refractory to hematinic therapy. Also, she was noted to have failure to thrive, developmental delay and epilepsy. She was referred to the Genetics clinic where whole-exome sequencing (WES) was done and showed a novel homozygous variant in the UMPS gene confirming a diagnosis of HOA. She was started on uridine triacetate after which she showed clinical, hematologic and biochemical improvement. Although extremely rare, hereditary orotic aciduria should be suspected in any child with megaloblastic bone marrow, immunodeficiency or when developmental delay and anemia coexist.http://www.sciencedirect.com/science/article/pii/S221442692030149XOrotic aciduriaUridine-5-monophosphate synthaseImmunodeficiency |
| spellingShingle | Hebah S. Al Absi Stephanie Sacharow Naser Al Zein Aisha Al Shamsi Amal Al Teneiji Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation Molecular Genetics and Metabolism Reports Orotic aciduria Uridine-5-monophosphate synthase Immunodeficiency |
| title | Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation |
| title_full | Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation |
| title_fullStr | Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation |
| title_full_unstemmed | Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation |
| title_short | Hereditary orotic aciduria (HOA): A novel uridine-5-monophosphate synthase (UMPS) mutation |
| title_sort | hereditary orotic aciduria hoa a novel uridine 5 monophosphate synthase umps mutation |
| topic | Orotic aciduria Uridine-5-monophosphate synthase Immunodeficiency |
| url | http://www.sciencedirect.com/science/article/pii/S221442692030149X |
| work_keys_str_mv | AT hebahsalabsi hereditaryoroticaciduriahoaanoveluridine5monophosphatesynthaseumpsmutation AT stephaniesacharow hereditaryoroticaciduriahoaanoveluridine5monophosphatesynthaseumpsmutation AT naseralzein hereditaryoroticaciduriahoaanoveluridine5monophosphatesynthaseumpsmutation AT aishaalshamsi hereditaryoroticaciduriahoaanoveluridine5monophosphatesynthaseumpsmutation AT amalalteneiji hereditaryoroticaciduriahoaanoveluridine5monophosphatesynthaseumpsmutation |