Background: Segawa syndrome due to GTP cyclohydrolase deficiency is an autosomal dominant disorder with variable expression, that is clinically characterised by L-dopa responsive, diurnally fluctuating dystonia and pa...Background: Segawa syndrome due to GTP cyclohydrolase deficiency is an autosomal dominant disorder with variable expression, that is clinically characterised by L-dopa responsive, diurnally fluctuating dystonia and parkinsonian symptoms. Objective: To delineate the neurological and psychiatric phenotype in all affected individuals of three extended families. Methods: GTP cyclohydrolase deficiency was documented by biochemical analyses, enzymatic measurements in fibroblasts, and molecular investigations. All affected individuals were examined neurologically, and psychiatric data were systematically reviewed. Results: Eighteen affected patients from three families with proven GTP cyclohydrolase deficiency were identified. Eight patients presenting at less than 20 years of age had typical motor symptoms of dystonia with diurnal variation. Five family members had late-presenting mild dopa-responsive symptoms of rigidity, frequent falls, and tendonitis. Among mutation carriers older than 20 years of age, major depressive disorder, often recurrent, and obsessive-compulsive disorder were strikingly more frequent than observed in the general population. Patients responded well to medication increasing serotonergic neurotransmission and to L-dopa substitution. Sleep disorders including difficulty in sleep onset and maintenance, excessive sleepiness, and frequent disturbing nightmares were present in 55% of patients. Conclusion: Physicians should be aware of this expanded phenotype in affected members of families with GTP cyclohydrolase deficiency.展开更多
伴皮质下梗死和白质脑病的常染色体隐性遗传性脑动脉病（cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy，CARASIL）是一种临床上以脱发、反复卒中发作、进行性认知水平下降以及颈椎、...伴皮质下梗死和白质脑病的常染色体隐性遗传性脑动脉病（cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy，CARASIL）是一种临床上以脱发、反复卒中发作、进行性认知水平下降以及颈椎、腰椎退行性变为主要特征的常染色体隐性遗传性疾病。展开更多
文摘Background: Segawa syndrome due to GTP cyclohydrolase deficiency is an autosomal dominant disorder with variable expression, that is clinically characterised by L-dopa responsive, diurnally fluctuating dystonia and parkinsonian symptoms. Objective: To delineate the neurological and psychiatric phenotype in all affected individuals of three extended families. Methods: GTP cyclohydrolase deficiency was documented by biochemical analyses, enzymatic measurements in fibroblasts, and molecular investigations. All affected individuals were examined neurologically, and psychiatric data were systematically reviewed. Results: Eighteen affected patients from three families with proven GTP cyclohydrolase deficiency were identified. Eight patients presenting at less than 20 years of age had typical motor symptoms of dystonia with diurnal variation. Five family members had late-presenting mild dopa-responsive symptoms of rigidity, frequent falls, and tendonitis. Among mutation carriers older than 20 years of age, major depressive disorder, often recurrent, and obsessive-compulsive disorder were strikingly more frequent than observed in the general population. Patients responded well to medication increasing serotonergic neurotransmission and to L-dopa substitution. Sleep disorders including difficulty in sleep onset and maintenance, excessive sleepiness, and frequent disturbing nightmares were present in 55% of patients. Conclusion: Physicians should be aware of this expanded phenotype in affected members of families with GTP cyclohydrolase deficiency.
文摘伴皮质下梗死和白质脑病的常染色体隐性遗传性脑动脉病（cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy，CARASIL）是一种临床上以脱发、反复卒中发作、进行性认知水平下降以及颈椎、腰椎退行性变为主要特征的常染色体隐性遗传性疾病。
