scholarly journals Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis

Brain ◽  
2010 ◽  
Vol 133 (6) ◽  
pp. 1810-1822 ◽  
Author(s):  
M. A. Willemsen ◽  
M. M. Verbeek ◽  
E.-J. Kamsteeg ◽  
J. F. de Rijk-van Andel ◽  
A. Aeby ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Hydroxylase Deficiency ◽  
Catecholamine Biosynthesis ◽  
Tyrosine Hydroxylase Deficiency

TYROSINE HYDROXYLASE DEFICIENCY

The Lancet ◽  
1971 ◽  
Vol 297 (7708) ◽  
pp. 1050-1051 ◽  
Author(s):  
WilliamE. Martin
Keyword(s):  
Tyrosine Hydroxylase ◽  
Hydroxylase Deficiency ◽  
Tyrosine Hydroxylase Deficiency

Tyrosine Hydroxylase Deficiency Presenting with a Biphasic Clinical Course

2007 ◽  
Vol 38 (4) ◽  
pp. 213-215 ◽  
Author(s):  
T. Giovanniello ◽  
V. Leuzzi ◽  
C. Carducci ◽  
C. Carducci ◽  
M. Sabato ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Clinical Course ◽  
Hydroxylase Deficiency ◽  
Tyrosine Hydroxylase Deficiency

Study of a fetal brain affected by a severe form of tyrosine hydroxylase deficiency, a rare cause of early parkinsonism

2015 ◽  
Vol 31 (3) ◽  
pp. 705-709 ◽  
Author(s):  
Alba Tristán-Noguero ◽  
Héctor Díez ◽  
Cristina Jou ◽  
Mercè Pineda ◽  
Aida Ormazábal ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Fetal Brain ◽  
Severe Form ◽  
Hydroxylase Deficiency ◽  
Tyrosine Hydroxylase Deficiency

O61 – 1802 Tyrosine hydroxylase deficiency. The Greek experience

2013 ◽  
Vol 17 ◽  
pp. S19-S20 ◽  
Author(s):  
R Pons ◽  
D Syrengelas ◽  
A Gkika ◽  
A Dinopoulos ◽  
I Orfanou ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Hydroxylase Deficiency ◽  
Tyrosine Hydroxylase Deficiency

scholarly journals Novel Mutations in the Tyrosine Hydroxylase Gene in the First Czech Patient with Tyrosine Hydroxylase Deficiency

2012 ◽  
Vol 113 (2) ◽  
pp. 136-146 ◽  
Author(s):  
K. Szentiványi ◽  
H. Hansíková ◽  
J. Krijt ◽  
K. Vinšová ◽  
M. Tesařová ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Psychomotor Retardation ◽  
Type B ◽  
Hydroxylase Deficiency ◽  
Excessive Sweating ◽  
Adequate Treatment ◽  
Age Related ◽  
Neurometabolic Disorders ◽  
Tyrosine Hydroxylase Deficiency ◽  
Neurotransmitter Metabolites

Tyrosine hydroxylase deficiency manifests mainly in early childhood and includes two clinical phenotypes: an infantile progressive hypokinetic-rigid syndrome with dystonia (type A) and a neonatal complex encephalopathy (type B). The biochemical diagnostics is exclusively based on the quantitative determination of the neurotransmitters or their metabolites in cerebrospinal fluid (CSF). The implementation of neurotransmitter analysis in clinical praxis is necessary for early diagnosis and adequate treatment. Neurotransmitter metabolites in CSF were analyzed in 82 children (at the age 1 month to 17 years) with clinical suspicion for neurometabolic disorders using high performance liquid chromatography (HPLC) with electrochemical detection. The CSF level of homovanillic acid (HVA) was markedly decreased in three children (64, 79 and 94 nmol/l) in comparison to age related controls (lower limit 218–450 nmol/l). Neurological findings including severe psychomotor retardation, quadruspasticity and microcephaly accompanied with marked dystonia, excessive sweating in the first patient was compatible with the diagnosis of tyrosine hydroxylase (TH) deficiency (type B) and subsequent molecular analysis revealed two novel heterozygous mutations c.636A>C and c.1124G>C in theTHgene. The treatment with L-DOPA/carbidopa resulted in the improvement of dystonia. Magnetic resonance imaging studies in two other patients with microcephaly revealed postischaemic brain damage, therefore secondary HVA deficit was considered in these children. Diagnostic work-up in patients with neurometabolic disorders should include analysis of neurotransmitter metabolites in CSF.

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

2021 ◽  
Vol 11 (11) ◽  
pp. 1186
Author(s):  
Gyrid Nygaard ◽  
Peter D. Szigetvari ◽  
Ann Kari Grindheim ◽  
Peter Ruoff ◽  
Aurora Martinez ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Status ◽  
Dopamine Synthesis ◽  
Hydroxylase Deficiency ◽  
Catecholamine Biosynthesis ◽  
Improve Treatment ◽  
Key Enzyme ◽  
Gch1 Gene

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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