Neurologic and psychiatric manifestations in a family with a mutation in exon 2 of the guanosine triphosphate-cyclohydrolase gene.
OBJECTIVE
To investigate the range of clinical features to correlate genotypic and phenotypic manifestations in hereditary progressive and/or levodopa-responsive dystonia due to a defect in the guanosine triphosphate-cyclohydrolase (GCH1) gene.


METHODS
A large family from Texas was studied in an ambulatory setting by clinicians in genetics, neurology, and psychiatry using structured interviews and examinations.


METHODS
The family was selected after neurometabolic investigations of a young boy (proband) with foot dystonia and fatigue and his father, who had a long history of anxiety and depression. Results of metabolic studies showed decreased levels of metabolites of biopterin and biogenic amines in cerebrospinal fluid. Subsequently, a novel mutation (37-base pair deletion) in exon 2 of the GCH1 gene was demonstrated in 11 family members. There was no observed female sex bias, but there was a wide variability of motor dysfunctions in family members. Approximately 50% had clinical deafness and a similar number had significant psychiatric dysfunction, including depression and anxiety.


CONCLUSIONS
Study of additional families with hereditary progressive and/or levodopa-responsive dystonia using modern molecular methods will be necessary to confirm the neuropsychiatric spectrum of this disorder, in which important clinical features may be unrecognized and thus inappropriately managed.
Hahn
H
H
Department of Neurology, PO Box 20708, Houston, TX 77225-0708, USA.
Trant
M R
MR
Brownstein
M J
MJ
Harper
R A
RA
Milstien
S
S
Butler
I J
IJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D001679:Biogenic Amines / Q000378:metabolism; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009422:Nervous System Diseases / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D011622:Pterins / Q000378:metabolism
D001679:Biogenic Amines; D011622:Pterins; D006136:GTP Cyclohydrolase