Clinical and Genetic Characteristics of Children with Dopa-Responsive Dystonia Due to Tyrosine Hydroxylase Deficiency
- VernacularTitle:酪氨酸羟化酶缺乏症导致多巴反应性肌张力不全患儿临床及遗传特点
- Author:
Hai-xia ZHU
1
;
Xiao-jing LI
1
;
Hui-ci LIANG
1
;
Wen-lin WU
1
;
Chi HOU
1
;
Lian-feng CHEN
1
;
Yang TIAN
1
;
Wen-xiong CHEN
1
Author Information
1. Neurology of Guangzhou Women and Children’s Medical Center， Guangzhou 510120， China
- Publication Type:Journal Article
- Keywords:
dopa-responsive dystonia;
tyrosine hydroxylase deficiency;
TH gene
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(2):307-312
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the clinical and genetic characteristics， treatment and prognosis of children with dopa-responsive dystonia due to tyrosine hydroxylase deficiency （THD）. MethodThe clinical data of 6 children with dopa-responsive dystonia due to THD， who were admitted to the Department of Neurology of Guangzhou Women and Children’s Medical Center from June 2017 to Nov 2020， were retrospectively analyzed. ResultsThese 6 children （4 boys and 2 girls）， who came from four different families， suffered from dystonia. The median age of onset was 11.5 months （range from 3 months to 4 years）. Compound heterozygous TH gene mutations were found in six patients. Seven different mutations were identified in the TH gene including five known mutations： c.698G>A（p.R233H）， c.1145T>C（p.I382T）， c.739G>A（p.G247S）， c.1481C>T（p.T494M）， c.880G>C（p.G294） and two novel mutations： c.1279A>G（p.Y427H） and c.1128_1138del（p.Q377GfsTer12）. The patients took different doses of Madopa， ranging from 2 to 15 mg/（kg·d） in maintenance. All the patients responded well to Madopa but Case 4 was left with scoliosis. ConclusionsTHD can cause a broad range of clinical symptoms and severity. Early identification and initiation of levodopa therapy significantly improved the prognosis. We here identified two novel heterozygous variant in TH（c.1279A>G and c.1128_1138del）. Our study expands the spectrum of genotype of THD in China， providing new insights into the molecular mechanism of THD. Genetic testing can make a definite diagnosis.
