Dados do Trabalho

Título

LEVODOPA-RESPONSIVE DYSTONIA (DYT5) IN A LARGE FAMILY FROM MINAS GERAIS: THE IMPORTANCE OF EARLY DIAGNOSIS

Introdução

Dopa-responsive dystonia associated with mutations in the GCH1 gene (DYT5) is classically described as autosomal dominant but rare cases with recessive inheritance have been reported. The autosomal dominant (AD) form is characterized by a childhood onset and predominates in the females. It usually starts with gait disturbance with foot dystonia (segmental dystonia) with fluctuation of symptoms during the day, and parkinsonism can be present. The treatment consists of low doses of levodopa and diagnosis is confirmed by the identification of pathogenic variant in the GCH1 gene.

Objetivo

To present a family with 7 affected individuals from a large family, originally from small city in Minas Gerais.

Métodos

All the affected members were clinically evaluated. Neuroimaging and molecular study were performed in the index case. The affected individuals were treated with L-dopa and followed from 2 to 5 years.

Resultados

The index case is a female who presented dystonia in right lower limb, at the age of 8 years old. The patient improved her symptoms with L-dopa treatment. The molecular study showed in a heterozygous pathogenic variant in exon 5 of the GCH1 gene (c.607G>A /p.Gly203Arg). A total of nine relatives of the index case that complaint of gait abnormalities was evaluated: 6 females and 3 males. All men did not have dystonia. The 6 females were: the daughter of the index case, who showed segmental dystonia (left foot) at 4 years of age; three first-degree cousins that showed segmental dystonia with the age of onset ranging from 8 - 23 years. More two older third-degree cousins (diagnosed at the age of 50 and 53 years) presented history of segmental dystonia that evolved to diffuse dystonia associated to parkinsonism, and they lost the capacity of walking at the age of 15 and 44 years, respectively. After starting levodopa, all women responded with improvement in walking. The two older relatives who lost the walk ability became able to walk with support, but their improvement was limited by contractures and foot deformities.

Conclusões

Early identification of individuals with dopa-responsive dystonia allows for timely initiation of levodopa therapy. The response to L-dopa could be observed in patients with long course of the disease however the joint contractures and foot deformities were the limiting factor for better results. In addition, through genetic diagnosis the family can be informed about the disease and genetic counseling.

Palavras chave

Dystonia, levodopa, GCH1

Referências (se houver)

Fonte de Fomento (se houver)

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Área

Neurogenética