in children with infantile parkinsonism-dystonia
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We have recently identified mutations in the dopamine
transporter gene, SLC6A3, for children with infantile
parkinsonism-dystonia with raised CSF metabolites (raised HVA with normal HIAA).
The mutations are novel and functional work shows loss of gene function (absent
dopamine reuptake). It is the first genetic link of DAT function linked to a
disorder with parkinsonian features.
We are now collecting cases of infantile parkinsonism dystonia (with raised HVA and normal HIAA) - so far I have a cohort of several cases and all have different mutations (missense, deletions, splice site mutations). In this work we are aiming to delineate the genetic and clinical aspects of this disorder.
As regards the phenotype - we are still trying to get a handle on this new disorder and our aim is to define it better genetically and clinically.
The phenotype may be wider than we currently know. So far, in the several families I have accrued who have mutations in SLC6A3, the phenotype is as follows:
Children are born after an uneventful pregnancy and birth although some had non-specific neonatal irritability and feeding difficulties. Presentation is in infancy generally between 3-6 months with symptoms of parkinsonism-dystonia - stiffening of the limbs, paucity of spontaneous limb movement with bradykinesia (tremor deos not seem to be a prominent feature) and generalised dystonia (affecting all 4 limbs, face, jaw and severe in nature). Pyramidal tract features then develop over the next 6-12 months. The children have axial hypotonia and some have head lag. A few children develop an eye movement disorder with ocular flutter and saccade initiation failure. Some of the children in the cohort were initially misdiagnosed as having CP. All children develop global developmental delay. Although we are still working on their neuropsychology status, it appears that disability is more physical than cognitive (one of the children attends mainstream school).
CSF HVA ranges between 1100 - over 3000 nmol/l.
CSF HIAA is normal.
Serum prolactin is raised.
If you have such a case we would be very happy to undertake gene sequencing (it is currently free as I am doing it on a research basis). Of note the study has full UK ethics approval.
Please contact either myself or Professor Eamonn Maher
manju_dave at hotmail.com
e.r.maher at bham.ac.uk
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Last revised 14-Jun-2009 by Steven Leber