Dihydrofolate Reductase Deficiency Due to a Homozygous DHFR Mutation Causes Megaloblastic Anemia and Cerebral Folate Deficiency Leading to Severe Neurologic Disease

• Published in: American journal of human genetics Vol. 88; no. 2; pp. 226 - 231
• Main Authors: Cario, Holger, Smith, Desirée E.C., Blom, Henk, Blau, Nenad, Bode, Harald, Holzmann, Karlheinz, Pannicke, Ulrich, Hopfner, Karl-Peter, Rump, Eva-Maria, Ayric, Zuleya, Kohne, Elisabeth, Debatin, Klaus-Michael, Smulders, Yvo, Schwarz, Klaus
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 11.02.2011; Cell Press; Elsevier
• Subjects: Anemia; Anemia, Megaloblastic - diagnosis; Anemia, Megaloblastic - genetics; Biological and medical sciences; Cells; Child; Child, Preschool; Chromatography; Chromosomes; Epilepsy; Erythrocytes - metabolism; Female; Fluoresceins - metabolism; Folic Acid - blood; Folic Acid - cerebrospinal fluid; Folic Acid Deficiency - blood; Folic Acid Deficiency - cerebrospinal fluid; Folic Acid Deficiency - diagnosis; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; Homozygote; Humans; Male; Medical genetics; Medical sciences; Metabolism; Methotrexate - analogs & derivatives; Methotrexate - metabolism; Models, Molecular; Molecular and cellular biology; Mutation; Mutation - genetics; Nervous System Diseases - diagnosis; Nervous System Diseases - genetics; Pedigree; Protein Conformation; Tetrahydrofolate Dehydrogenase - chemistry; Tetrahydrofolate Dehydrogenase - deficiency; Tetrahydrofolate Dehydrogenase - genetics; Vitamin B; Vitamin deficiency; Human; Nervous system diseases; Megaloblastic anemia; Enzyme; Critically ill; Deficiency; Hemopathy; Homozygosity; Folate; Encephalon; Genetics; Oxidoreductases; Dihydrofolate reductase; Mutation

The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral f...