Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes

Fernández-Ramos, J.A.; Torre-Aguilar, María José de la; Quintáns, Beatriz; Pérez-Navero, Juan Luís; Beyer, Katrin; López‐Laso, Eduardo; Sepúlveda, J.J. Ochoa; Cárdenas, J. Serrano; Gómez, M.J. Sobrido; MORA, MARÍA DEL ROSARIO VALLEJO; Moreno-Medinilla, E.; Ramos, Juana; Llorente, Marta; Teva, M.D.; Martínez-Ruiz, J.; Gutiérrez-Solana, Luis González; Martín, Maite; Gómez‐Esteban, Juan Carlos; Hernández‐Vara, Jorge; Cazorla, Angeles Garcia; Artuch, Rafael; Adarmes, Astrid; Mir, Pablo

doi:10.1016/j.parkreldis.2021.11.014

Parkinsonism & Related Disorders

2022

DOI: 10.1016/j.parkreldis.2021.11.014

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Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes

J.A. Fernández-Ramos

María José de la Torre-Aguilar

Beatriz Quintáns

et al.

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Cited by 3 publications

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Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes

Novelli,

Tolve,

Quiroz

et al. 2024

Movement Disord Clin Pract

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BackgroundThe GCH1 gene encodes the enzyme guanosine triphosphate cyclohydrolase I (GTPCH), which catalyzes the rate‐limiting step in the biosynthesis of tetrahydrobiopterin (BH4), a critical cofactor in the production of monoamine neurotransmitters. Autosomal dominant GTPCH (adGTPCH) deficiency is the most common cause of dopa‐responsive dystonia (DRD), whereas the recessive form (arGTPCH) is an ultrarare and poorly characterized disorder with earlier and more complex presentation that may disrupt neurodevelopmental processes. Here, we delineated the phenotypic spectrum of ARGTPCHD and investigated the predictive value of biochemical and genetic correlates for disease outcome.ObjectivesThe aim was to study 4 new cases of arGTPCH deficiency and systematically review patients reported in the literature.MethodsClinical, biochemical, and genetic data and treatment response of 45 patients are presented.ResultsThree phenotypes were outlined: (1) early‐infantile encephalopathic phenotype with profound disability (24 of 45 patients), (2) dystonia‐parkinsonism phenotype with infantile/early‐childhood onset of developmental stagnation/regression preceding the emergence of movement disorder (7 of 45), and (3) late‐onset DRD phenotype (14 of 45). All 3 phenotypes were responsive to pharmacological treatment, which for the first 2 must be initiated early to prevent disabling neurodevelopmental outcomes. A gradient of BH4 defect and genetic variant severity characterizes the 3 clinical subgroups. Hyperphenylalaninemia was not observed in the second and third groups and was associated with a higher likelihood of intellectual disability.ConclusionsThe clinical spectrum of arGTPCH deficiency is a continuum from early‐onset encephalopathies to classical DRD. Genotype and biochemical alterations may allow early diagnosis and predict clinical severity. Early treatment remains critical, especially for the most severe patients.

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Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes

Novelli,

Tolve,

Quiroz

et al. 2024

Movement Disord Clin Pract

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Phenotypes and Genotypes of Inherited Disorders of Biogenic Amine Neurotransmitter Metabolism

Mastrangelo

Tolve

Artiola

et al. 2023

Genes

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Inherited disorders of biogenic amine metabolism are genetically determined conditions resulting in dysfunctions or lack of enzymes involved in the synthesis, degradation, or transport of dopamine, serotonin, adrenaline/noradrenaline, and their metabolites or defects of their cofactor or chaperone biosynthesis. They represent a group of treatable diseases presenting with complex patterns of movement disorders (dystonia, oculogyric crises, severe/hypokinetic syndrome, myoclonic jerks, and tremors) associated with a delay in the emergence of postural reactions, global development delay, and autonomic dysregulation. The earlier the disease manifests, the more severe and widespread the impaired motor functions. Diagnosis mainly depends on measuring neurotransmitter metabolites in cerebrospinal fluid that may address the genetic confirmation. Correlations between the severity of phenotypes and genotypes may vary remarkably among the different diseases. Traditional pharmacological strategies are not disease-modifying in most cases. Gene therapy has provided promising results in patients with DYT-DDC and in vitro models of DYT/PARK-SLC6A3. The rarity of these diseases, combined with limited knowledge of their clinical, biochemical, and molecular genetic features, frequently leads to misdiagnosis or significant diagnostic delays. This review provides updates on these aspects with a final outlook on future perspectives.

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Dopa Responsive Dystonia with Marked Diurnal Fluctuation (Sagawa Disease) Forty-Five Years of Follow–Up

2024

J Psychol Neurosci

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Objective: To describe the clinical course and very long personal follow-up of a patient with Segawa Disease Methods: The medical records of the patient since the diagnosis at the age of 9 years until her last follow-up at the age of 55 years were obtained and summarized Results: The long-term follow-up showed an excellent long-lasting response to L-DOPA therapy and also revealed that non-motor psychiatric features are an integral part of the disease rather than an emotional side effect of chronic motor disability. Conclusion: Long term follow-up of Segawa syndrome can provide additional information on prognosis and quality of life in old age, which are not known yet.

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Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes

Cited by 3 publications

References 26 publications

Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes

Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes

Phenotypes and Genotypes of Inherited Disorders of Biogenic Amine Neurotransmitter Metabolism

Dopa Responsive Dystonia with Marked Diurnal Fluctuation (Sagawa Disease) Forty-Five Years of Follow–Up

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