Abstract
We describe a disease encompassing infantile-onset movement disorder (including severe parkinsonism and nonambulation), mood disturbance, autonomic instability, and developmental delay, and we describe evidence supporting its causation by a mutation in SLC18A2 (which encodes vesicular monoamine transporter 2 [VMAT2]). VMAT2 translocates dopamine and serotonin into synaptic vesicles and is essential for motor control, stable mood, and autonomic function. Treatment with levodopa was associated with worsening, whereas treatment with direct dopamine agonists was followed by immediate ambulation, near-complete correction of the movement disorder, and resumption of development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Age of Onset
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Base Sequence
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Benzothiazoles / therapeutic use
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Chromosomes, Human, Pair 10
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Dopamine / metabolism*
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Dopamine / urine
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Dopamine Agonists / therapeutic use
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Dopamine Plasma Membrane Transport Proteins / metabolism
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Dystonia / genetics
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Female
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Humans
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Infant
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Male
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Molecular Sequence Data
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Mood Disorders / genetics*
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Movement Disorders / drug therapy
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Movement Disorders / genetics*
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Mutation*
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Parkinsonian Disorders / genetics
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Pedigree
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Pramipexole
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Sequence Analysis, DNA
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Serotonin / metabolism*
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Serotonin Plasma Membrane Transport Proteins / metabolism
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Syndrome
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Vesicular Monoamine Transport Proteins / genetics*
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Vesicular Monoamine Transport Proteins / metabolism
Substances
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Benzothiazoles
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Dopamine Agonists
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Dopamine Plasma Membrane Transport Proteins
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Serotonin Plasma Membrane Transport Proteins
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Vesicular Monoamine Transport Proteins
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Serotonin
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Pramipexole
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Dopamine