AUTOSOMAL DOMINANT GTP CYCLOHYDROLASE I DEFICIENCY

Objective: Autosomal Dominant GTP cyclohydrolase I Deficiency (Segawa disease) is a postural dystonia with onset in childhood. This presentation describes the clinical characteristics, pathophysiology and etiological considerations.

Methods: Analyses of clinical and neurophysiological features on the patients of this clinic were presented.

Results: Classical features are childhood onset postural dystonia starting in the leg with diurnal fluctuation of symptoms. Postural tremor appears in early teens and becomes apparent after midteens or in the third decades. No parkinsonian tremor is seen. Interlimb coordination is preserved. No autonomic nervous symptoms or psychobehavioral symptoms are seen. The symptoms progress in the first two decades but then stabilize. Along with the course diurnal variation decreases the grade and becomes unapparent in the third decade. Adult onset cases starts with tremor and gait disturbance without dystonia and diurnal fluctuation. Levodopa shows marked effect, which sustains lifelong without side effects. The causative gene, GTP cyclohydrolase I (GCH I) gene, mutation is found in over 80% of classical cases. After the gene was detected the phenotypical variations are found, including action dystonia, focal dystonia, paroxysmal dystonia, dystonic spasm with or without pain and oculogyric crisis. Muscle hypotonia with delay in crawling and language developmental delay are observed in compound heterozygote cases. Psychobehavioral disorders such as autism and depression, and migraine were also reported. Some of them depend on the loci of mutation and the grade of involvement of the serotonergic neurons.

Conclusion: Segawa disease is the first inherited dystonia whose causative gene was found. The clinical features, pathophysiology and gene mutations have been clarified. The effect of levodopa is usually complete. However, some cases are still misdiagnosed as the other diseases. Careful clinical analyses with consideration of pathophysiology are necessary when dystonia case is presented.

Keywords: postural dystonia, childhood, diurnal fluctuation, levodopa