Brain dopamine-serotonin vesicular transport disease presenting as a severe infantile hypotonic parkinsonian disorder.
Two male siblings from a consanguineous union presented in early infancy with marked truncal hypotonia, a general paucity of movement, extrapyramidal signs and cognitive delay. By mid-childhood they had made little developmental progress and remained severely hypotonic and bradykinetic. They developed epilepsy and had problems with autonomic dysfunction and oculogyric crises. They had a number of orthopaedic problems secondary to their hypotonia. Cerebrospinal fluid (CSF) neurotransmitters were initially normal, apart from mildly elevated 5-hydroxyindolacetic acid, and the children did not respond favourably to a trial of levodopa-carbidopa. The youngest died from respiratory complications at 10 years of age. Repeat CSF neurotransmitters in the older sibling at eight years of age showed slightly low homovanillic acid and 5-hydroxyindoleacetic acid levels. Whole-exome sequencing revealed a novel mutation homozygous in both children in the monoamine transporter gene SLC18A2 (p.Pro237His), resulting in brain dopamine-serotonin vesicular transport disease. This is the second family to be described with a mutation in this gene. Treatment with the dopamine agonist pramipexole in the surviving child resulted in mild improvements in alertness, communication, and eye movements. This case supports the identification of the causal mutation in the original case, expands the clinical phenotype of brain dopamine-serotonin vesicular transport disease and confirms that pramipexole treatment may lead to symptomatic improvement in affected individuals.
Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Jessie C
JC
Jacobsen
Adult and Paediatric National Metabolic Service, Auckland City Hospital, Auckland, New Zealand.
Callum
C
Wilson
Child Health Centre, Northland District Health Board, Whangarei, New Zealand.
Vicki
V
Cunningham
Adult and Paediatric National Metabolic Service, Auckland City Hospital, Auckland, New Zealand.
Emma
E
Glamuzina
Diagnostic Genetics, LabPLUS, Auckland City Hospital, Auckland, New Zealand.
Debra O
DO
Prosser
Diagnostic Genetics, LabPLUS, Auckland City Hospital, Auckland, New Zealand.
Donald R
DR
Love
VCGS Pathology, Murdoch Childrens' Research Institute, Parkville, Victoria, Australia.
Trent
T
Burgess
Genetic Health Service New Zealand, Auckland City Hospital, Auckland, New Zealand.
Juliet
J
Taylor
Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Brendan
B
Swan
Department of Neurology, Auckland City Hospital, Auckland, New Zealand.
Rosamund
R
Hill
Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Stephen P
SP
Robertson
Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland, New Zealand. r.snell@auckland.ac.nz.
Russell G
RG
Snell
Centre for Brain Research and School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Klaus
K
Lehnert
D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001927:Brain Diseases / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D002230:Carbidopa / Q000627:therapeutic use; D002648:Child; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*
D012701:Serotonin; D007980:Levodopa; D002230:Carbidopa; D004298:Dopamine