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
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.
Nygaard T, Duvoisin R: Hereditary dystonia-parkinsonism syndrome of
juvenile onset. Neurology
Priscu V, Lurie S, Savir I, et al: The choice of anesthesia in Segawa's syndrome. ...