Levodopa-Responsive Aromatic L-Amino Acid Decarboxylase Deficiency

Yuh Terng Chang; Radhakant Sharma; J. Lawrence Marsh; John Douglas Mcpherson; Joey A. Bedell; Andreas Knust; Christa Bräutigam; Georg F. Hoffmann; Keith Hyland

doi:10.1002/ana.20055

Levodopa-Responsive Aromatic L-Amino Acid Decarboxylase Deficiency

Yuh Terng Chang, Radhakant Sharma, J. Lawrence Marsh, John Douglas Mcpherson, Joey A. Bedell, Andreas Knust, Christa Bräutigam, Georg F. Hoffmann, Keith Hyland

Research output: Contribution to journal › Article

33 Scopus citations

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.

Original language	English (US)
Pages (from-to)	435-438
Number of pages	4
Journal	Annals of Neurology
Volume	55
Issue number	3
DOIs	https://doi.org/10.1002/ana.20055
State	Published - Mar 2004
Externally published	Yes

ASJC Scopus subject areas

Neuroscience(all)

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Chang, Y. T., Sharma, R., Marsh, J. L., Mcpherson, J. D., Bedell, J. A., Knust, A., Bräutigam, C., Hoffmann, G. F., & Hyland, K. (2004). Levodopa-Responsive Aromatic L-Amino Acid Decarboxylase Deficiency. Annals of Neurology, 55(3), 435-438. https://doi.org/10.1002/ana.20055

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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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AU - Mcpherson, John Douglas

AU - Bedell, Joey A.

AU - Knust, Andreas

AU - Bräutigam, Christa

AU - Hoffmann, Georg F.

AU - Hyland, Keith

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