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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adolescent
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Adult
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Alanine / genetics
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Antiparkinson Agents / therapeutic use*
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Aromatic-L-Amino-Acid Decarboxylases / chemistry
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Aromatic-L-Amino-Acid Decarboxylases / deficiency*
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Aromatic-L-Amino-Acid Decarboxylases / drug effects
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Binding Sites / drug effects
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Carbidopa / therapeutic use
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Chromatography, High Pressure Liquid
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DNA Mutational Analysis
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Developmental Disabilities / drug therapy*
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Developmental Disabilities / genetics
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Drug Combinations
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Electrochemistry
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Family Health
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Female
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Glycine / genetics
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Humans
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Levodopa / therapeutic use*
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Male
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Models, Structural
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Point Mutation
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Protein Binding
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Protein Conformation / drug effects
Substances
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Antiparkinson Agents
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Drug Combinations
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Levodopa
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Aromatic-L-Amino-Acid Decarboxylases
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Carbidopa
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Alanine
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Glycine