Levodopa-responsive aromatic L-amino acid decarboxylase deficiency.
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.
Kimberly H. Courtwright and Joseph W. Summers Institute of Metabolic Disease, Baylor University Medical Center, 3812 Elm Street, Dallas, TX 75226, USA.
Yuh Terng
YT
Chang
Radhakant
R
Sharma
J Lawrence
JL
Marsh
John D
JD
McPherson
Joey A
JA
Bedell
Andreas
A
Knust
Christa
C
Bräutigam
Georg F
GF
Hoffmann
Keith
K
Hyland
D000293:Adolescent; D000328:Adult; D000409:Alanine / Q000235:genetics; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000737:chemistry / Q000172:deficiency* / Q000187:drug effects; D001665:Binding Sites / Q000187:drug effects; D002230:Carbidopa / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000188:drug therapy* / Q000235:genetics; D004338:Drug Combinations; D004563:Electrochemistry; D005192:Family Health; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008961:Models, Structural; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects
D000978:Antiparkinson Agents; D004338:Drug Combinations; D007980:Levodopa; D001142:Aromatic-L-Amino-Acid Decarboxylases; D002230:Carbidopa; D000409:Alanine; D005998:Glycine