Brain dopamine-serotonin vesicular transport disease and its treatment.
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.
Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Jennifer J
JJ
Rilstone
Reem A
RA
Alkhater
Berge A
BA
Minassian
D017668:Age of Onset; D001483:Base Sequence; D052160:Benzothiazoles / Q000627:therapeutic use; D002879:Chromosomes, Human, Pair 10; D004298:Dopamine / Q000378:metabolism* / Q000652:urine; D018491:Dopamine Agonists / Q000627:therapeutic use; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004421:Dystonia / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D019964:Mood Disorders / Q000235:genetics*; D009069:Movement Disorders / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D020734:Parkinsonian Disorders / Q000235:genetics; D010375:Pedigree; D000077487:Pramipexole; D017422:Sequence Analysis, DNA; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D013577:Syndrome; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics* / Q000378:metabolism
D052160:Benzothiazoles; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D012701:Serotonin; D000077487:Pramipexole; D004298:Dopamine