Levodopa-responsive aromatic L-amino acid decarboxylase deficiency.

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