Consensus Guideline for the Diagnosis and Treatment of Tyrosine Hydroxylase ( <scp>TH</scp> ) 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 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.

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Publication Details

Journal
Journal of Inherited Metabolic Disease
Published
2025-11-01
DOI
https://doi.org/10.1002/jimd.70106
Citations
1
Primary Topic
Metabolism and Genetic Disorders
Type
article
Field-Weighted Citation Impact
1.32

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article

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

Roser Pons, Tessa Wassenberg, Manju A. Kurian, Oya Kuseyri Hübschmann et al.
1 citations
Journal of Inherited Metabolic Disease
Metabolism and Genetic Disorders
1.32
article

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

Roser Pons, Tessa Wassenberg, Manju A. Kurian, Oya Kuseyri Hübschmann, Mario Mastrangelo, Thomas Opladen, Agathe Roubertie, Vincenzo Leuzzi, Mariya Sigatullina Bondarenko, Ángeles García‐Cazorla, Mariarita Bertoldi, Ivana Badnjarevic, Kathrin Jeltsch, Jan Kulhánek, Toni S. Pearson, Galina Stevanović, Elisenda Cortès‐Saladelafont, Gabriella Horváth, Birgit Assmann
article en
1 citations

Abstract

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.

Journal of Inherited Metabolic DiseaseVol. 48(6)
University of Verona (IT), Hospital Sant Joan de Déu Barcelona (ES), Nationwide Children's Hospital (US), University of Novi Sad (RS), National and Kapodistrian University of Athens (GR), Charles University (CZ), Heidelberg University (DE), Great Ormond Street Hospital (GB), Policlinico Umberto I (IT), University Hospital Heidelberg (DE), Vancouver General Hospital (CA), Hospital Son Llatzer (ES), Centre Hospitalier Universitaire de Montpellier (FR), Center for Children (US), Universitair Ziekenhuis Brussel (BE), University Children's Hospital, Belgrade (RS), BC Children's Hospital (CA), Hospital Universitari Germans Trias i Pujol (ES), General University Hospital in Prague (CZ), University College London (GB), Heidelberg University (US), Sapienza University of Rome (IT)
Silicon Valley Community Foundation, Fundació la Marató de TV3, Instituto de Salud Carlos III, European Regional Development Fund
Openalex Percentile: Top 14%
Metabolism and Genetic Disorders
1.32
DOIOpen Access PDFOpenAlex
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