Identification and characterization of an inborn error of metabolism caused by dihydrofolate reductase deficiency
SourceAmerican Journal of Human Genetics, 88, 2, (2011), pp. 216-25
Article / Letter to editor
Display more detailsDisplay less details
Laboratory of Genetic, Endocrine and Metabolic Diseases
Paediatrics - OUD tm 2017
American Journal of Human Genetics
SubjectDCN 1: Perception and Action IGMD 4: Glycostation disorders; DCN 3: Neuroinformatics; IGMD 3: Genomic disorders and inherited multi-system disorders; NCMLS 6: Genetics and epigenetic pathways of disease IGMD 3: Genomic disorders and inherited multi-system disorders
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.
This item appears in the following Collection(s)
- Academic publications 
- Faculty of Medical Sciences 
Upload full text
Use your RU credentials (u/z-number and password) to log in with SURFconext to upload a file for processing by the repository team.