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At a glance

Described as a rare movement disorder that typically begins in childhood and is characterized by a triad of dystonic postures, parkinsonism, and marked and sustained response to low-dose levodopa therapy.

Synonyms

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

Incidence

Very rare, female/male ratio 4:1.

Genetic inheritance

Autosomal recessive inheritance and autosomal dominant forms have been described.

Pathophysiology

The autosomal dominant form (>80%) is due to a mutation on GCH-1 gene on 14q22.1-q22.2 which encodes GTP-cyclohydrolase 1 which is involved in the synthesis of tetrahydrobiopterin (BH4), an essential cofactor for tyrosine hydroxylase, 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. The autosomal recessive form is due to a mutation on 11p15, which encodes the tyrosine hydroxylase.

Diagnosis

Historical and clinical features. Measurement of tyrosine hydroxylase and GTP-cyclohydrolase 1 activity. Low concentration of the dopamine metabolite homovanillic acid (HVA) in cerebrospinal fluid.

Clinical aspects

Predominantly occurs in females. Characterized by postural and motor disturbances with marked diurnal fluctuation. Onset is usually in early childhood (<6 years) 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.

Precautions before anesthesia

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

Anesthetic considerations

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.

Pharmacological implications

Should continue L-dopa or anticholinergic medication through the perioperative period. Use direct vasopressors (phenylephrine) as response to indirect (ephedrine) is reduced. Succinylcholine appears to be safe. Avoid central dopamine antagonists (metoclopramide) for risk of dystonia.

References

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Howze  KE, Will  ND, Klassen  BT,  et al: Anesthetic implications for patients with Segawa syndrome. J Clin Anesth 35:350, 2016.  [PubMed: 27871555]
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Nygaard  T, Duvoisin  R: Hereditary dystonia-parkinsonism syndrome of juvenile onset. Neurology 36:1424, 1986.  [PubMed: 3762960]
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Priscu  V, Lurie  S, Savir  I,  et al: The choice of ...

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