Compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive dopa-responsive dystonia

Abstract

Rationale:Autosomal-recessive dopa-responsive dystonia (DRD) is a rare clinical disorder presenting as bradykinesia, dystonia, tremor and even severe encephalopathy, and caused by tyrosine hydroxylase deficiency (THD). We report a case of compound heterozygous mutations in the TH gene in a Chinese family with autosomal-recessive DRD herein.Patient concerns:A 16-month-old Chinese boy presented with symptoms of movement disorder and growth retardation in his infant period.Diagnoses:The genetic test revealed compound heterozygous mutations in the TH gene at c.457C>T and c.698G>A, which are pathogenic of DRD.Interventions:The patient was administrated low-dose levodopa.Outcomes:The treatment resulted in the substantial improvement of dystonia. His long-term neurological outcome need follow-up for years.Lessons:Gene mutation analysis is helpful and necessary to diagnose DRD and has important guiding significance for the subsequent treatment.

Dopa-responsive dystonia caused by tyrosine hydroxylase deficiency

“…We reviewed all cases of THD reported through 2018 and have summarized the features of the 87 cases found. [ 7 – 44 ] The age at onset ranged from the neonatal period to 18 years of age, and the average onset age was 13.4 months. The clinical features reported for 75 cases are described in Table 1 .…”

R233H mutation in patients with tyrosine hydroxylase deficiency and corresponding phenotypes: a study of four cases and literature review

“…We analyzed the clinical manifestations, diagnosis, and treatment of the 4 patients diagnosed with TH deficiency at Beijing Tiantan Hospital (Table 1, Ref. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]), . To obtain data on all patients with R233H mutation in TH deficiency reported to date, we searched Medline, PubMed, China National Knowledge Infrastructure (ht tp://www.cnki.net), and Wanfang Data (http://www.wanf angdata.com.cn) databases for papers published in English or Chinese up to August 2020.…”

“…Among all 42 patients, there were 19 males and 14 females, and 9 for which gender was unknown (Table 1, Ref. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]). There were 22 patients with Type A TH deficiency, 17 patients with severe Type B TH deficiency, and the phenotype of remaining 2 patients was not clear.…”

“…In recent years, TH deficiency has been diag-nosed with increasing frequency. Direct mutation analysis has been performed in more than 100 TH deficiency patients, and R233H is the most frequent mutation, with 21 patients of 53 from China and 21 patients from the remaining other countries carrying this mutation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. This mutation is a G to A transversion at amino-acid position 698, resulting in histidine instead of arginine within the highly conserved domain of the TH protein, that is thought to interfere with the normal functioning of the TH protein.…”

“…A total of 42 patients with a mutation in R233H could be analyzed, including 21 patients from China (Table 1, Ref. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]). Meanwhile, in this study, we reviewed the clinical features, treatment, and prognosis of four patients with homozygous mutation of R233H in TH at our hospital.…”