Objective: To describe the clinical phenotype and genetic characteristics of a novel mutation causing Segawa´s disease in a Spanish family.

Background: Dopa-Responsive Dystonia (DRD) is a group of clinically and genetically heterogeneous disorders characterized by limb onset abnormal postures with marked diurnal fluctuations showing a sustained and excellent response to L-dopa. The most common condition leading to DRD is heterozygous mutations of the GTP ciclohydrolase 1 gene, located on 14q22.1-q22.2, also named  Segawa´s disease. GTP ciclohydrolase I mutations alter the central biosynthesis of dopamine

Method: Review the clinical recordings and genetic characteristics of two related subjects affected by Segawa´s disease from a Spanish family.

Results: Case 1: This is a 45 year-old woman. Psychomotor development was normal. Her disease started at the age of 2 and a half  when parents noticed frequent falls and progressive gait difficulties. Gait worsened progressively with shuffling gait and instability. At the age of 7 , she noticed bilateral postural and action tremor. At this moment neurologic examination revealed a shuffling gait with dystonic posture (bilateral equinovarus). Deep tendon reflexes were brisk with aquileous clonus. The severity of clinical features fluctuated markedly throughout the day with benefit from the sleep. CSF levels of biopterin, 5-HIAA and HVA were normal. No abnormalities were detected on Cranial and Spinal MRI. L-dopa was prescribed  (50 mg per day) with a marked and sustained response.Case 2: This is a 70 year-old man. His neurological picture started at the age of 40,  characterized by a progressive impairment of gait. At this moment exploration revealed mild dystonic posture of the lower limb and brisk deep tendon reflexes. Gait clearly worsened throughout the day and patient also referred benefit from sleep. CSF levels of biopterin, 5-HIAA and HVA were normal. Cranial and Spinal MRI were unremarkable. L-dopa was prescribed (200 mg per day) with a marked response.A genetic test revealed a heterozygous point mutation p.W53X (c.158G>A) at Exon 1. This mutation leads to a codon stop and a trunked protein.

Conclusion: Here we described a previous not reported mutation on GTP ciclohydrolase 1 gene in a Spanish family widening the genotypic spectrum. However, clinical features were indistinguishable of the classical Segawa´s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-genetic-characteristics-of-a-new-mutation-causing-segawas-disease-in-a-spanish-kindred/