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. DESIGN AND SETTING: A large family from Texas was studied in an ambulatory setting by clinicians in genetics, neurology, and psychiatry using structured interviews and examinations. PATIENTS: 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. CONCLUSION: 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.
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. DESIGN AND SETTING: A large family from Texas was studied in an ambulatory setting by clinicians in genetics, neurology, and psychiatry using structured interviews and examinations. PATIENTS: 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. CONCLUSION: 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.
Authors: J L K Van Hove; J Steyaert; G Matthijs; E Legius; P Theys; R Wevers; A Romstad; L B Møller; K Hedrich; D Goriounov; N Blau; C Klein; P Casaer Journal: J Neurol Neurosurg Psychiatry Date: 2006-01 Impact factor: 10.154
Authors: Eduardo López-Laso; Araceli Sánchez-Raya; Juan Antonio Moriana; Eduardo Martínez-Gual; Rafael Camino-León; María Elena Mateos-González; Juan Luis Pérez-Navero; Juan José Ochoa-Sepúlveda; Aida Ormazabal; Thomas Opladen; Christine Klein; José Ignacio Lao-Villadóniga; Katrin Beyer; Rafael Artuch Journal: J Neurol Date: 2011-05-10 Impact factor: 4.849
Authors: Mary Ann Richardson; Laura L Read; Margaret A Reilly; James D Clelland; Catherine L Taylor Clelland Journal: Neurochem Res Date: 2006-12-09 Impact factor: 3.996
Authors: C Wider; S Melquist; M Hauf; A Solida; S A Cobb; J M Kachergus; J Gass; K D Coon; M Baker; A Cannon; D A Stephan; D F Schorderet; J Ghika; P R Burkhard; G Kapatos; M Hutton; M J Farrer; Z K Wszolek; F J G Vingerhoets Journal: Neurology Date: 2007-09-05 Impact factor: 9.910