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.
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Authors | Yuh Terng Chang, Radhakant Sharma, J Lawrence Marsh, John D McPherson, Joey A Bedell, Andreas Knust, Christa Bräutigam, Georg F Hoffmann, Keith Hyland |
Journal | Annals of neurology
(Ann Neurol)
Vol. 55
Issue 3
Pg. 435-8
(Mar 2004)
ISSN: 0364-5134 [Print] United States |
PMID | 14991824
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Antiparkinson Agents
- Drug Combinations
- Levodopa
- Aromatic-L-Amino-Acid Decarboxylases
- Carbidopa
- Alanine
- Glycine
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Topics |
- Adolescent
- Adult
- Alanine
(genetics)
- Antiparkinson Agents
(therapeutic use)
- Aromatic-L-Amino-Acid Decarboxylases
(chemistry, deficiency, drug effects)
- Binding Sites
(drug effects)
- Carbidopa
(therapeutic use)
- Chromatography, High Pressure Liquid
- DNA Mutational Analysis
- Developmental Disabilities
(drug therapy, genetics)
- Drug Combinations
- Electrochemistry
- Family Health
- Female
- Glycine
(genetics)
- Humans
- Levodopa
(therapeutic use)
- Male
- Models, Structural
- Point Mutation
- Protein Binding
- Protein Conformation
(drug effects)
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