| Title | Levodopa-responsive aromatic L-amino acid decarboxylase deficiency. |
| Publication Type | Journal Article |
| Year of Publication | 2004 |
| Authors | Chang, YTerng, Sharma, R, J Marsh, L, McPherson, JD, Bedell, JA, Knust, A, Bräutigam, C, Hoffmann, GF, Hyland, K |
| Journal | Ann Neurol |
| Volume | 55 |
| Issue | 3 |
| Pagination | 435-8 |
| Date Published | 2004 Mar |
| ISSN | 0364-5134 |
| Keywords | Adolescent, Adult, Alanine, Antiparkinson Agents, Aromatic-L-Amino-Acid Decarboxylases, Binding Sites, Carbidopa, Chromatography, High Pressure Liquid, Developmental Disabilities, DNA Mutational Analysis, Drug Combinations, Electrochemistry, Family Health, Female, Glycine, Humans, Levodopa, Male, Models, Structural, Point Mutation, Protein Binding, Protein Conformation |
| Abstract | We report three siblings, who were treated empirically with levodopa combined with carbidopa. There was an immediate therapeutic response. Biochemical investigation surprisingly showed the clinical phenotype to be caused by aromatic L-amino acid decarboxylase deficiency. Molecular characterization showed a homozygous point mutation (c.387 G-->A) in exon 3. Kinetic studies showed the mutation to decrease the binding affinity for the substrate. This, combined with structural modeling suggesting alteration of active site configuration, provided an explanation for the therapeutic response to levodopa. |
| DOI | 10.1002/ana.20055 |
| Alternate Journal | Ann Neurol |
| PubMed ID | 14991824 |
| Grant List | R01 HD 36049 / HD / NICHD NIH HHS / United States R01 HD 36081 / HD / NICHD NIH HHS / United States |