Segawa Syndrome

Described by the presence of jerky movement at the age of 3 months. It is associated with generalized rigidity and no diurnal variability. Evolving rapidly to expressionless face, ptosis, drooling, and tremulous tongue movements. Usually associated with a low concentration of the dopamine metabolite homovanillic acid (HVA) in the cerebrospinal fluid.

Parkinsonism Infantile; Dystonia 5; Dystonia-Parkinsonism with Diurnal Fluctuation; Dopa-Responsive Dystonia; Tyrosine Hydroxylase Deficiency.

Autosomal recessive inheritance. An autosomal dominant form of this clinical entity has also been described. In this case, it is believed to be caused by a mutation in the GCH1 gene. A linkage has been found between Segawa syndrome and a point mutation in exon 11 of the tyrosine hydroxylase (TH) gene resulting in a gin381-to-lys exchange.

Evidence of a mutation in the GTP-cyclohydrolase 1 gene, causing limited conversion of GTP to BH4 (tetrahydrobiopterin). BH4 is a cofactor for tyrosine hydroxylase, which is the rate-limiting step in dopamine synthesis. These patients may produce BH4 at a rate that is insufficient to compensate for the normal consumption of the cofactor during the day, leading to aggravation of symptoms toward the evening.

Historical and clinical features. Measurement of tyrosine hydroxylase and GTP-cyclohydroxylase 1 activity. Genetic mapping for GTP-cyclohydroxlase 1 on chromosome 14q.

Predominantly occurs in females. Characterized by postural and motor disturbances with marked diurnal fluctuation. Onset is usually in early childhood presenting with lower limbs and axial dystonia, followed by parkinsonism. Commonly the inversion and plantar flexion of feet can be seen early in association with increasing flexion of the hip and the knee, resulting in a toe-walking gait. Both flexor and extensor posture of the arms may occur. Posture reflex is impaired. Slowly progressive parkinsonian features include slowed movement, muscle rigidity, and balance difficulty. Symptoms are remarkable and are alleviated after sleep and aggravated toward the evening. Response to a small dose of l-dopa is immediate and most often associated with dramatic improvement. The coexistence of parkinsonian features and the dramatic response to l-dopa distinguish this syndrome from other forms of idiopathic torsion dystonia. The sustained nature of l-dopa responsiveness and the lack of complications from therapy (including wearing-off, “on-off” and unpredictable dose response) distinguish it from other causes of childhood-onset parkinsonism.

Complete neurological examination and documentation must be obtained in symptomatic patients. The hydration status must be assessed.

No reported complications. The potential for intraoperative labile blood pressure, particularly with postural changes during surgery, must be carefully monitored. Fluid management must be ensured to prevent the possibility of volume depletion. Care in positioning of patient.

Should continue l-dopa or anticholinergic medication through the perioperative period.