Consensus Guideline for the Diagnosis and Treatment of Tyrosine Hydroxylase (TH) Deficiency

Tyrosine hydroxylase (TH) catalyses the rate-limiting step in dopamine biosynthesis. Autosomal recessive tyrosine hydroxylase deficiency (THD) leads to clinical phenotypes reflecting the deficiency of dopamine, norepinephrine, or epinephrine in the central nervous system (CNS), presenting along a co...

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Detalles Bibliográficos
Autores: Bondarenko, Mariya Sigatullina, Hübschmann, Oya Kuseyri, Kulhánek, Jan, Pons, Roser, Pearson, Toni S, Jeltsch, Kathrin, Badnjarevic, Ivana, Wassenberg, Tessa, Horvath, Gabriella, Stevanovic, Galina, Kurian, Manju A, Cortès-Saladelafont, Elisenda, Roubertie, Agathe, Leuzzi, Vincenzo, Bertoldi, Mariarita, Mastrangelo, Mario, Assmann, Birgit, Garcia-Cazorla, Angeles, Opladen, Thomas
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/26242
Acceso en línea:https://hdl.handle.net/20.500.13003/26242
Access Level:acceso abierto
Palabra clave:Dystonia
Neurotransmitter Agents
Tyrosine
Distonía
Neurotransmisores
Tirosina
dopa‐responsive dystonia
international working group on neurotransmitter related disorders
neurotransmitter
tyrosine hydroxylase deficiency
Descripción
Sumario:Tyrosine hydroxylase (TH) catalyses the rate-limiting step in dopamine biosynthesis. Autosomal recessive tyrosine hydroxylase deficiency (THD) leads to clinical phenotypes reflecting the deficiency of dopamine, norepinephrine, or epinephrine in the central nervous system (CNS), presenting along a continuous spectrum from mild to severe forms of the disease. The diagnosis is suggested by the detection of low CSF homovanillic acid (HVA) and confirmed by identifying biallelic pathogenic variants in the TH gene. L-dopa/decarboxylase inhibitor (DCI) supplementation is often the first-line treatment, and most patients have a good therapeutic response. However, initiation of therapy can be challenging in patients with severe disease forms who develop L-dopa/DCI-induced dyskinesia. Therefore, alternative treatment options, such as monoamine oxidase (MAO) inhibitors, must be evaluated to optimize motor symptom control. Clinical experience suggests that early diagnosis and treatment initiation may improve the outcome. Additionally, a multidisciplinary treatment approach should be utilized to monitor neurocognitive development and other comorbidities that may occur in THD. In this consensus guideline, representatives of the International Working Group on Neurotransmitter related Disorders (iNTD) and patient advocates evaluated all the evidence available in the literature on the diagnosis and management of THD and developed recommendations using the SIGN and GRADE methodologies. Based on the limited evidence, practical recommendations have been developed to support clinical diagnosis, laboratory testing, neuroimaging, medical treatment, and non-medical interventions. Research topics for further development were identified. This guideline aims to improve the care of patients with THD worldwide and raise general awareness of this rare disease.