Identification and Characterization of an Inborn Error of Metabolism Caused by Dihydrofolate Reductase Deficiency
| Autor: | Robert Steinfeld, Henk J. Blom, Desirée E.C. Smith, Simon Jones, William G. Newman, Jill E. Urquhart, Yvo M. Smulders, Christopher M. Clouthier, Grace Vassallo, Emma Hilton, Yanick J. Crow, Joelle N. Pelletier, John H. Walter, Ron A. Wevers, Majid Aziz, Siddharth Banka, Simon Heales, Arjan P.M. de Brouwer, Andrew Will, Gillian I. Rice |
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| Přispěvatelé: | Laboratory Medicine, Internal medicine, ICaR - Ischemia and repair |
| Rok vydání: | 2011 |
| Předmět: |
Male
Models Molecular Anemia Megaloblastic Pancytopenia Protein Conformation Leucovorin Neuroinformatics [DCN 3] chemistry.chemical_compound 0302 clinical medicine Dihydrofolate reductase Missense mutation Genetics(clinical) heterocyclic compounds Genetics (clinical) 0303 health sciences biology Brain Tetrahydrobiopterin Magnetic Resonance Imaging Pedigree 3. Good health Biochemistry Female medicine.drug medicine.medical_specialty Anemia Molecular Sequence Data Biopterin Folic Acid Deficiency Genomic disorders and inherited multi-system disorders [IGMD 3] 03 medical and health sciences Folic Acid Report Internal medicine parasitic diseases medicine Genetics Humans Amino Acid Sequence Megaloblastic anemia Amino Acid Metabolism Inborn Errors Tetrahydrobiopterin deficiency 030304 developmental biology Base Sequence Sequence Homology Amino Acid Infant medicine.disease Tetrahydrofolate Dehydrogenase Endocrinology chemistry Inborn error of metabolism biology.protein Perception and Action Glycostation disorders [DCN 1] Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6] 030217 neurology & neurosurgery |
| Zdroj: | American journal of human genetics, 88(2), 216-225. Cell Press American Journal of Human Genetics, 88, 216-25 Banka, S, Blom, H J, Walter, J, Aziz, M, Urquhart, J, Clouthier, C M, Rice, G I, de Brouwer, A P M, Hilton, E, Vassallo, G, Will, A, Smith, D E C, Smulders, Y M, Wevers, R A, Steinfeld, R, Heales, S, Crow, Y J, Pelletier, J N, Jones, S & Newman, W G 2011, ' Identification and Characterization of an Inborn Error of Metabolism Caused by Dihydrofolate Reductase Deficiency ', American journal of human genetics, vol. 88, no. 2, pp. 216-225 . https://doi.org/10.1016/j.ajhg.2011.01.004 American Journal of Human Genetics, 88, 2, pp. 216-25 |
| ISSN: | 0002-9297 |
| Popis: | Item does not contain fulltext Dihydrofolate reductase (DHFR) is a critical enzyme in folate metabolism and an important target of antineoplastic, antimicrobial, and antiinflammatory drugs. We describe three individuals from two families with a recessive inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency due to a germline missense mutation in DHFR, resulting in profound enzyme deficiency. We show that cerebral folate levels, anemia, and pancytopenia of DHFR deficiency can be corrected by treatment with folinic acid. The characterization of this disorder provides evidence for the link between DHFR and metabolism of cerebral tetrahydrobiopterin, which is required for the formation of dopamine, serotonin, and norepinephrine and for the hydroxylation of aromatic amino acids. Moreover, this relationship provides insight into the role of folates in neurological conditions, including depression, Alzheimer disease, and Parkinson disease. |
| Databáze: | OpenAIRE |
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