(Hereditary progressive dystonia with diurnal fluctuations, dopa-responsive dystonia, infantile parkinsonism, DYT5).

Very rare. Congenital deficit of the synthesis of dopamine leading to a form of early-onset parkinson disease responsive to low doses of levodopa.

Several forms:

-        DYT5a: the most frequent form. Autosomal dominant transmission (> 80 %) of a mutation of the  GCH-1 gene (14q22.1-q22.2) [MIM 128 230]; this gene codes for GTP-cyclohydrolase 1, involved in the synthesis of tetrahydrobiopterin (BH4), an essential cofactor for tyrosine hydroxylase, the enzyme limiting the synthesis of dopamine.

-        DYT5b: form with autosomal recessive transmission of a mutation of the TH gene (tyrosine hydroxylase) (11p15) [MIM 605 405] or of the SPR gene (2p13.2) causing a deficiency in sepiapterin reductase [MIM 612 716]: the  onset is earlier and clinical course more severe .

It usually starts around the age of 6 years by dystonic movements of a foot and later of the lower limbs. The upper limbs are affected later. These movements are fluctuating and usually more marked at the end of the day or after an exercise. Girls and young women are more affected than boys (4/1). There is sometimes a postural tremor.

The administration of low L-dopa doses has a spectacular and constant effect over time.

Anesthetic implications:

the treatment with L-dopa should be administered up to the morning of anesthesia; risk of dysphagia and gastroparesis; central dopamine antagonists should be avoided: butyrophenones, metoclopramide. Although no data exist for this disease, chronic use of L-dopa may induce orthostatic hypotension and a decrease in the response to indirect vasopressors like ephedrine. It is therefore preferable to use direct vasopressors such as phenylephrine but reported cases do not mention any adverse reaction.

References : 

-        Priscu V, Lurie S, Savir I, Rabinerson D, Hagay Z. 
The choice of anesthesia in Segawa’s syndrome. 
J Clin Anesth 1998; 1: 153-5

-         Sinha A, Hartsilver EL. 
Anaesthesia for caesarean section in a patient with dopa-responsive dystonia or Segawa’ syndrome. 
Int J Obstetr Anaesth 2009; 18: 67-72.

-        Warnecke T, Fiedler F.
Anaesthesia and orphan disease: a septuagenarian patient with Segawa’s dystonia.
Eur J Anaesthesiol 2015 ; 32 : 889-91.

-        Howze KE, Will ND, Klassen BT, Sprung J, Weingarten TN.
Anesthetic implications for patients with Segawa syndrome.
J Clin Anesth 2016; 35: 350-7.

-        Opladen T, Lopez-Laso E, Cortes-Saladelafont E, Pearson TS, Sivri HS et al.
Consensus guidelines for the diagnosis and treatment of tetrahydrobiopterin (BH4) deficiencies.
Orphanet J Rare Diseases 2020; 15:126

Updated: July 2020