Segawa syndrome
| Classification according to ICD-10 | |
|---|---|
| G24.8 | Other dystonia |
| ICD-10 online (WHO version 2019) | |
The Segawa syndrome ( L -Dopa-sensitive or responsive dystonia, DRD ) is a very rare genetic disease . It is a generalized idiopathic dystonia (torsional dystonia). It was first recognized in 1970 by the Japanese neurologist Masaya Segawa as an independent clinical picture.
Etiology and Genetics
From a molecular genetic point of view, it is a defect in the GCH1 gene ( GTP cyclohydrolase I ) on the long arm of chromosome 14 gene locus q22.1 – q22.2. GCH-I is the rate-limiting enzyme in the synthesis of tetrahydrobiopterins (BH4). The classic biochemical defect is therefore a deficiency in tetrahydrobiopterin. Tetrahydrobiopterin is u. a. needed in the body to make levodopa (L-DOPA).
The mode of inheritance is autosomal - dominant with variable penetrance , or autosomal recessive . Mutations in the tyrosine hydroxylase gene and in the parkin gene lead to similar phenotypic manifestations .
The incidence is difficult to assess because of the rarity of this disease. It is roughly estimated at 1 case per 5 million children. The female sex seems to be slightly preferred. The time of first manifestation is usually in the first decade of life between the ages of 4 and 8. Occasionally, however, patients do not become symptomatic until early adulthood, when the disease often occurs as focal dystonia.
Symptoms
The disease begins with a gait disorder. The feet are in dystonic flexion and inward position. Initially, the symptoms are fluctuating, but in the course of the disease this abnormal position of the legs can become so fixed that walking becomes practically impossible. In addition, Parkinson's syndrome can develop as the disease progresses . Other neurological complaints are less common.
diagnosis
Anamnesis is an important diagnostic criterion . It turns out that the disorder is less pronounced after a sleep phase and more pronounced after physical exertion. The symptoms typically increase as the day progresses. Some children go to school in the morning carefree and can no longer leave it without outside help. The second typical feature is that the dystonia responds well to even low doses of levodopa .
If the patient becomes symptomatic in early childhood, it can be confused with infantile cerebral palsy (Little's disease).
therapy
There is no cure for the disease, but it can be treated well. It is the only dystonia that can be treated causally. An important prerequisite for this is good patient compliance , since the medication must be taken long-term and without interruption.
Treatment is with levodopa . This substance is well tolerated by the affected patients.
literature
- M. Segawa: Autosomal dominant GTP cyclohydrolase I (AD GCH 1) deficiency (Segawa disease, dystonia 5; DYT 5). (PDF; 911 kB) In: Chang Gung medical journal. Volume 32, Number 1, 2009 Jan.-Feb., Pp. 1-11, ISSN 2072-0939 . PMID 19292934 . (Review).
- M. Segawa, Y. Nomura, N. Nishiyama: Autosomal dominant guanosine triphosphate cyclohydrolase I deficiency (Segawa disease). In: Annals of neurology. Volume 54 Suppl 6, 2003, pp. S32-S45, ISSN 0364-5134 . doi : 10.1002 / ana.10630 . PMID 12891652 . (Review).
Individual evidence
- ^ Segawa syndrome. In: Online Mendelian Inheritance in Man . (English).
- ^ Segawa syndrome. In: Orphanet (Rare Disease Database).
