Tyrosine hydroxylase deficiency—Clinical insights and a novel deletion in <i>TH</i> gene in an Indian patient

Bijarnia‐Mahay, Sunita; Jain, Vivek; Thöny, Beat

doi:10.1002/jmd2.12111

Cited by 4 publications

(2 citation statements)

References 9 publications

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“…We compiled the summary from Dong et al, encompassing all TH deficiency cases reported through 2018 (Dong et al, 2020) and all Segawa patients published thereafter until 2023 (Atanasoska et al, 2023; Bijarnia‐Mahay et al, 2020; Champagne et al, 2022; Chen et al, 2020; Couto et al, 2019; Hou et al, 2019; Hull et al, 2021; Janssen et al, 2021; Kuseyri Hubschmann et al, 2021; Panda et al, 2022; Reyes et al, 2023; Wang et al, 2022). In total, we summarized the clinical phenotypes of all 175 reported Segawa cases.…”

Section: Case Presentationmentioning

confidence: 99%

Compound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes

Zhang,

Huang,

et al. 2024

Intl J of Devlp Neuroscience

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Segawa syndrome is a rare autosomal recessive form of dopa‐responsive dystonia resulting from TH gene dysfunction. Patients typically exhibit symptoms such as generalized dystonia, rigidity, tremors, infantile Parkinsonism, and pseudo‐spastic paraplegia. Levodopa is often an effective treatment. Due to its rarity, high heterogeneity, and poorly understood pathological mutation and phenotype spectrums, as well as genotype–phenotype and genotype‐treatment outcome correlations, Segawa syndrome poses diagnostic and therapeutic challenges. In our study, through clinical and molecular analyses of three Chinese Segawa patients, we re‐evaluated the pathogenicity of a TH mutation (c.880G>C;p.G294R) previously categorized as “Conflicting classifications of pathogenicity” in ClinVar. Also, we summarized the clinical phenotypes of all reported Segawa syndrome cases until 2023 and compared them with our patients. We identified a novel phenotype, “cafe‐au‐lait macules,” not previously observed in Segawa patients. Additionally, we discussed the correlation between specific genotypes and phenotypes, as well as genotypes and treatment outcomes of our three cases. Our findings aim to enhance the understanding of Segawa syndrome, contributing to improved diagnosis and treatment approaches in the future.

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Section: Case Presentationmentioning

confidence: 99%

Compound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes

Zhang,

Huang,

et al. 2024

Intl J of Devlp Neuroscience

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“…Underdiagnosis is a major issue with THD and differential diagnosis include epilepsy [22], cerebral palsy [22], and vitamin B12-deficiency related infantile tremor syndrome [23] among others. It is important to reach a correct diagnosis at an early stage, as many patients are responsive to treatment.…”

Section: Diagnosing Thdmentioning

confidence: 99%

Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia—A Focus on Tyrosine Hydroxylase Deficiency

Nygaard

Szigetvari

Grindheim

et al. 2021

JPM

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Dopa-responsive dystonia (DRD) is a rare movement disorder associated with defective dopamine synthesis. This impairment may be due to the fact of a deficiency in GTP cyclohydrolase I (GTPCHI, GCH1 gene), sepiapterin reductase (SR), tyrosine hydroxylase (TH), or 6-pyruvoyl tetrahydrobiopterin synthase (PTPS) enzyme functions. Mutations in GCH1 are most frequent, whereas fewer cases have been reported for individual SR-, PTP synthase-, and TH deficiencies. Although termed DRD, a subset of patients responds poorly to L-DOPA. As this is regularly observed in severe cases of TH deficiency (THD), there is an urgent demand for more adequate or personalized treatment options. TH is a key enzyme that catalyzes the rate-limiting step in catecholamine biosynthesis, and THD patients often present with complex and variable phenotypes, which results in frequent misdiagnosis and lack of appropriate treatment. In this expert opinion review, we focus on THD pathophysiology and ongoing efforts to develop novel therapeutics for this rare disorder. We also describe how different modeling approaches can be used to improve genotype to phenotype predictions and to develop in silico testing of treatment strategies. We further discuss the current status of mathematical modeling of catecholamine synthesis and how such models can be used together with biochemical data to improve treatment of DRD patients.

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Levodopa/carbidopa

2020

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Tyrosine hydroxylase deficiency—Clinical insights and a novel deletion in TH gene in an Indian patient

Cited by 4 publications

References 9 publications

Compound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes

Compound heterozygous mutations in three Chinese patients of Segawa syndrome and their treatment outcomes

Personalized Medicine to Improve Treatment of Dopa-Responsive Dystonia—A Focus on Tyrosine Hydroxylase Deficiency

Levodopa/carbidopa

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