Clinical features of Huntington disease in 243 Chinese patients★○
Xiaoyan Guo1, Shushan Zhang1, Jean-Marc Burgunder○2, Huifang Shang1

1Department of Neurology, West China Hospital, Sichuan University, Chengdu  610041, Sichuan Province, China
2Department of Neurology, Inselspital, Bern University, CH-3010 Bern, Switzerland

Xiaoyan Guo★, Studying for master’s degree, Department of Neurology, West China Hospital, Sichuan   University, Chengdu  610041, Sichuan Province, China

Corresponding author: Huifang Shang, Doctor, Associated professor, Department of Neurology, West China Hospital, Sichuan University, Chengdu   610041, Sichuan Province, China   
hfshang@yahoo.com

Abstract
OBJECTIVE: To thoroughly explore the clinical characteristics of Huntington disease in China.
METHODS: A computer-based online search of China National Knowledge Infrastructure was performed to review case reports concerning Huntington disease published between 1980 and 2008; the clinical characteristics were analyzed.
RESULTS: A total of 80 studies involving 243 patients (142 males and 101 females) were collected, 82.0% of which were from provinces of North China. In addition, 97.1% of the cases had a family history of Huntington disease, and paternal inheritance (64.6%) was greater than maternal inheritance (35.4%). Moreover, onset age was significantly less than from maternal inheritance. The mean onset age of Huntington disease was (35.2 ± 11.5) years, mean age of death was (45.6 ± 13.5) years, and the mean course of disease from onset to death was (11.6 ± 5.6) years. Onset characterized by involuntary movement accounted for 47.7%, including 66.4% in the entire body, 16.4% in the upper limbs, and 14.7% in the head and face. Psychiatric symptoms accounted for 18.1%, and disturbed intelligence accounted for 2.1%. With disease progression, 99.5% of patients exhibited involuntary movement, 69.8% displayed cognitive impairment, and 39.2% suffered from psychiatric symptoms. In addition, 38.7% of patients were complicated by dysarthria, dysphagia, and cough after drinking. A total of 70.8% of patients exhibited an abnormal electroencephalogram, 18.8% had mild abnormalities in the cerebrospinal fluid, and 70.1% displayed brain atrophy and lateral ventriculomegaly on CT or MRI. A total of 88.9% of patients scored ≤ 23 in the Mini-Mental State Examination (MMSE). Of the reported patients, only 22 underwent IT15 gene testing with positive results.
CONCLUSION: Huntington disease is more frequently detected in males than females, and the majority has a family history. The disease has high incidence in Northern China, in particular with paternal inheritance. In addition, the disease often struck middle-aged people, and the time of onset in paternal inheritance was earlier than maternal inheritance. There were no significant differences in age of onset between males and females, and the course of disease was not related to paternal or maternal inheritance. The symptoms of onset included involuntary movement, complicated by psychiatric symptoms, and rarely cognitive impairment. In addition, involuntary movement of the pharynx was commonly observed in patients. Genetic detection has been the gold standard for clinical diagnosis of Huntington disease, and more attention should be paid to this detection method. 
Key Words: Huntington disease; clinical characteristics; literature evaluation; neurodegenerative disease

INTRODUCTION
  
Huntington disease (HD), also termed he-reditary chorea, chronic progressive chorea, or hysterical chorea, is an autosomal domi-nant-inherited disease. It is characterized by basal ganglia and cerebral cortex degenera-tion, as well as clinical features, such as pro-gressive chorea-like movement, mental symptoms, and dementia. A newly discov-ered gene, IT15, which was isolated by cloned trapped exons from the target area, has been shown to contain a polymorphic trinucleotide repeat, which is expanded and unstable on HD chromosomes and is re-garded as the genetic determinant for HD[1]. To date, very few case reports of HD exist in China, and most of the published work has included individual case reports. The present study aimed to further the understanding of HD through thorough analysis of clinical fea-tures of HD in China by retrieving HD reports in China and analyzing the clinical manifesta-tions.

MATERIALS AND METHODS

Subjects
Data inclusion and exclusion criteria
Pre-indexing did not reveal any system evaluations, prospective cohort studies, retrospective cohort studies, bioecological studies, or non-consecutive cohort studies regarding HD in China. Case or individual reports published between January 1st, 1980 and December 31st, 2008 were included, and reviews and experimental studies of HD 
were excluded.
Subject inclusion criteria
Currently in China, the gold standard for HD diagnosis has been defined by > 36 CAG trinucleotide repeats at the 5' end of the IT15 gene. However, precise diagnostic stan-dards were not found in the case reports of Chinese HD, and gene detection was rarely used for diagnosis. Accord-ing to the retrieval results, the inclusion criteria were for-mulated by combining Chinese and foreign reports, as well as clinical experiences: (1) involuntary movement, (2) dis-turbance of intelligence, (3) psychiatric symptoms, (4) brain atrophy confirmed by CT or MRI, (5) family history, and (6) positive gene detection. Case reports with non-definite di-agnosis or repetitive contents were excluded.
Retrieval methods
Huntington disease, hereditary chorea, chronic progres-sive chorea, and hysterical chorea were used as key-words to search related articles published between 1980 and 2008 in the China National Knowledge Infrastruc-ture.
Data extraction
The region, age, site, and symptoms of onset, clinical manifestation, and auxiliary examinations of each patient were extracted and recorded. The frequency of occur-rence of clinical manifestations was calculated and ana-lyzed.

RESULTS

Literature inclusion
A total of 213 articles related to HD were collected; 57 were excluded due to identical references, and 76 basic studies and repetitive reports were excluded; 80 studies involving 547 patients were selected[2-81]. Of these, 304 cases were excluded due to incomplete clinical data. In total, 243 HD patients were included (142 males and 101 females), with an age of onset of 7–70 years. Of these cases, 236 cases (97.1%) included a family history, but diagnostic standards were not mentioned. A total of 89 patients were noted to have come from a precise region, 16 were from the South, and the remainder were from the North (82.0%), including 15 from Henan Province, 14 from Shandong Province, and 8 from Hebei Province. The general characteristics of in-cluded articles are listed in Table 1.
 

 
Clinical manifestations (Table 2)

Onset was commonly observed in middle-aged patients, with a mean age of onset of (35.2 ± 11.5) years, mean death age of (45.6 ± 13.5) years (range 13–69 years), and mean course from onset to death of (11.6 ± 5.6) years (range 3–30 years). The study included 99 fami-lies. Paternal inheritance was greater than maternal inheritance, and age of onset of paternal inheritance was significantly less than maternal inheritance (P < 0.05). The age of death [(46.1 ± 15.1) years vs. (50.8 ± 10.0) years] and the course of disease [(12.0 ± 5.9) years vs. (11.9 ± 4.4) years] were not significantly dif-ferent (P > 0.05) between paternal inheritance and material inheritance. In addition, no significant differ-ences were found between male and female patients in terms of age of onset (Table 2), death age [(47.3 ± 14.5) years vs. (45.6 ± 12.1) years] and course of disease [(12.2 ± 6.0) years vs. (10.7 ± 5.0) years]  (P > 0.05). Within the cohort, 55 patients died, of which three were due to suicide.
Clinical manifestations were characterized by involuntary movement, disturbance of intelligence, and psychiatric symptoms. There were 212 patients with detailed clinical manifestation records: one displayed speech impairment, instability of gait and hypophrenia, with no obvious in-voluntary movement[68]; 146 cases (68.9%) suffered from involuntary movement complicated by cognitive decline; 82 (38.7%) had involuntary movement in limbs compli-cated by psychiatric symptoms; 60 cases (28.3%) had involuntary movement, cognitive decline, and psychiatric symptoms; 35 (16.5%) had involuntary movement in limbs, complicated by cognitive decline, dysarthria, dys-phagia, and cough after drinking; 34 patients (16.0%) suffered from involuntary movement in limbs, compli-cated by cognitive decline and psychiatric symptoms; and 26 patients (12.3%) had involuntary movement in limbs and cognitive decline, complicated by psychiatric symptoms, as well as dysarthria, dysphagia, and cough after drinking.
Laboratory examinations
In a total of 48 patients undergoing electroencephalo-grams, 34 (70.8%) presented with abnormal results and 32 of these were mildly abnormal. In a total of 16 patients undergoing cerebrospinal fluid examination, three (18.8%) displayed abnormally increased protein levels. In a total of 77 patients undergoing cranial imaging, 68 (88.3%) presented with abnormalities of varying extents, including 54 (70.1%) with brain atrophy and lateral ven-triculomegaly, one with caudate nucleus atrophy, and 13 (16.9%) with brain atrophy, lateral ventriculomegaly, and caudate nucleus atrophy. In a total of nine patients sub-jected to the Mini-Mental State Examination (MMSE), eight (88.9%) scored ≤ 23, and only one was normal (25 points). IT15 gene detection was positive in 22 patients, of which CAG repeats were clearly reported in 16 of the cases. The number of CAG repeats were greater in pa-tients with a younger age of onset: mean number of pa-tients younger than 30 years old was 60.8, with 48.1 in patients older than 30 years.

DISCUSSION

HD is a neurodegenerative disorder with autosomal dominant-inheritance. It is clinically characterized by involuntary chorea-like movement, asynergic movement, cognitive decline, and mental abnormalities. The inci-dence of HD in white people is very high, approximately (5–7)/100 000[82]. However, the disease is rarely diag-nosed in China, and no related epidemiological data has been reported.
Studies have shown that the incidence of HD is higher in Northern China, with 1.41-fold more male patients than female patients. The mean age of onset is (35.2 ± 11.5) years, which is consistent with reports from other areas of the world[83]. However, significant differences between male and female at age of onset, death age, or course of disease were not observed, which was different from other studies, reported a longer course of disease and survival in female patients[84]. The majority of patients had a family history, and only five cases were determined to be sporadic. Moreover, the number of cases due to paternal inheritance was significantly greater than from maternal inheritance, with a significantly younger age of onset with paternal inheritance, which was in accordance with previously published results[85]. In addition, the symptoms of onset predominantly included involuntary movement, consistent with other reports[86]. In particular, involuntary movement of the entire body was most commonly reported, with rare reports of involuntary movement of the lower limbs. Some patients exhibited psychiatric symptoms, and rare cases suffered from cognitive decline. Of the included patients, only one case presented with epilepsy, which was not consistent with previous reports showing 30% of adolescent HD com-plicated by epilepsy[87]. Clinical manifestations demon-strated that involuntary movement, cognitive decline, and psychiatric symptoms always occurred simultaneously. In particular, involuntary movement of the limbs, was de-tected in almost all patients. A total of 38.7% of patients presented with complications including pharynx involun-tary movement-induced dysarthria, dysphagia, and cough after drinking. Only nine patients had MMSE scores, and eight exhibited abnormalities, indicating that MMSE should be performed in future clinical diagnosis to improve the diagnostic rate of early cognitive decline. Psychiatric symptoms were seldom observed in HD pa-tients.
Except for gene detection, the auxiliary examinations were not specific to HD, but they could exclude chorea caused by other diseases. Gene detection could be util-ized to confirm HD. However, few patients underwent gene detection in China. Of the reported 22 patients that underwent IT15 gene detection, all were positive. The number of CAG repeats was reported in 16 of the cases, which suggested that younger the age of onset corre-lated with a greater number of CAG repeats, which was consistent with previous studies[88-89]. The mean number of patients younger than 30 years was 60.8, supporting previous studies reporting a greater number of CAG re-peats in patients younger than 20 years, compared with patients older than 30[90].
To date, studies involving the molecular mechanisms of HD and treatment have advanced. However, effective medical treatment to delay or inhibit progression remains unavailable. The United States approved the use of tetrabenazine, and was used to treat chorea-like symp-toms of HD in 2008[91]. If the patients experienced psy-chiatric symptoms, they were treated with tranquilizers, such as haloperidol or olanzapine. If they experienced depression, anti-depressants, such as paroxetine and fluoxetine, were used. Levodopa and pramipexole have been used to attenuate Parkinson disease-like symp-toms, and sodium valproate and clonazepam have been shown to ameliorate myoclonia and epilepsy. Creatoxin has been used to treat dysmyotonia, and acetylcholine esterase inhibitors, such as rivastigmine hydrogen tar-trate and galantamine, have been shown to improve cognitive functions. In addition, surgical therapies, such as deep-brain stimulation, improve chorea-like move-ments short-term, but long-term efficacy requires further investigation. The success rate of fetal cell transplanta-tion also remains uncertain, due to the lack of dou-ble-blinded comparisons with large sample sizes. Cal-cium antagonists, gene therapy, and virus-mediated transgenic nutrition factor may become effective meth-ods for treating HD[92]. Studies have suggested that the suicide rate of HD patients is significantly greater than healthy individuals, in particular in early or advanced stages[93], with 0.5–12.7% in the United States[87]. How-ever, in China, data regarding suicide is not available. In the present study, three patients died of suicide, due to non-tolerance symptoms. This indicated that health education and social support are extremely important for patients.
HD patients occasionally exhibit similar symptoms to Wilson’s disease, such as benign hereditary chorea, Anthony’s dance, and chorea-acanthocytosis. Therefore, diagnosis often requires gene detection. Early, correct diagnosis and medical treatment could provide better control for clinical symptoms of patients, and improve the quality of life. HD is a progressive disease. Therefore, a better understanding, early diagnosis, and genetic counseling remain important. The present study compiled literature from China over the past 20 years, and reviewed clinical data from 243 cases to provide primary reference for understanding HD features in Chinese to improve the early diagnosis rate. Nevertheless, this is a retrospective study, and only case reports with a score of grade IV were included. Because of the limitations, these results should only serve as clinical references.

REFERENCES

[1] The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell. 1993;72(6): 971-983.
[2] Gao WC. A case of Huntington’s disease. Bengbu Yixueyuan Xuebao. 1980;5(1):66-67.
[3] Liu LD, Xu YX, Liu BB. Two cases of Huntington’s disease. Zhongguo Shenjing Jingshen Jibing Zazhi. 1980;6(2):128.
[4] Li WS, Luan SL. The survey of one family with Huntington’s disease. Zhongguo Shenjing Jingshen Jibing Zazhi. 1980;6(5): 292-295.
[5] Wu XY. Two cases of Huntington’s disease. Shaanxi Yixue Zazhi. 1983;12(5):41-42.
[6] Xu Q, Qi JB, Han RH. A family survey of Huntington’s disease. Harbin Yiyao. 1983;3(2):75-77.
[7] Chen ZA. Two cases of Huntington’s disease with lithium carbonate treatment. Tianjin Yiyao. 1984;12(4):242-243.
[8] Du XL, Cui XH. A case report of Huntington’s disease. Ningxia Yixueyuan Xuebao. 1985;7(3):15-16.
[9] Feng JX. A case report of Huntington’s disease-with family survey. Zhongguo Shiyong Neike Zazhi. 1985;5(7):397.
[10] Fang SY, Li ZS, Li YH, et al. A four generation family of Huntington’s disease. Zhengzhou Daxue Xuebao: Yixue Ban. 1985;20(4):308-309.
[11] Wang GQ, Zhou GZ, Yao LZ, et al. An analysis of four families with Huntington’s disease. Shanghai Yixue. 1986;9(2):90-92.
[12] Fu HL, Mao ZB, Peng DQ, et al. A survey and assessment of amino acids level in serum of three families with Huntington’s disease. Jiangxi Yixueyuan Xuebao. 1986;26(4):83-87.
[13] Shao H. A case report of Huntington’s disease. Xin Yixue. 1986;17(2):77-78.
[14] Chen WJ, Xu DR. An analysis of a family with Huntington’s disease. Huanan Guofang Yixue Zazhi. 1987;1(3):91-92.
[15] Pei SC. A case report and family survey of Huntington’s disease. Lanzhou Daxue Xuebao: Yixue Ban. 1988;14(1):56-57.
[16] Bu SQ, Hou HG. A report of two families with Huntington’s disease. Jiangsu Yiyao. 1988;14(4):226-227.
[17] Ding KQ, Wang WH. Following up study of patients with IT15 gene carriers by EEG. Huazhong Shifan Daxue Xuebao: Ziran Kexue Ban. 1988;22(3):363-365.
[18] Ha ZY. A family report of Huntington’s disease with abnormal chromosome. Zhongguo Shenjing Jingshen Jibing Zazhi. 1988; 14(2):82.
[19] Xing YQ, Wu ZM, Chen FC. Five cases of Huntington’s disease. Guangdong Yixueyuan Xuebao. 1989;7(4):350-351.
[20] Tu XS. A case report of Huntington’s disease. Linchuang Neike Zazhi. 1989;6(20):111.
[21] Shao FY, Zai CH, Dou LP. A case report of Huntington’s disease presenting rigidity. Zhongguo Shenjing Jingshen Jibing Zazhi. 1989;(2):114.
[22] Xu YX, Liu MP. Three cases of Huntington’s disease. Weifang Yixueyuan Xuebao. 1990;12(4):72-73.
[23] Wu CD. A case report of patient with Huntington’s disease with initial symptom of mental disorder. Linchuang Shenjingbing Xue Zazhi. 1990;3(2):125-126.
[24] Huang JX. Four cases of Huntington’s disease in one family. Zhongguo Yousheng yu Yichuan Zazhi. 1990;10(4):89-90.
[25] Zeng ZX, Zhang JL. A family survey of Huntington’s disease. Zhongguo Yejin Gongye Yixue Zazhi. 1991;8(1):43.
[26] Fan K, Zhao TC, Feng LY. Twelve cases of Huntington’s disease in one family. Linchuang Shenjingbingxue Zazhi. 1992;5(3): 176-177.
[27] Sun CD, Wang HS, Yue SZ, et al. A family survey of Huntington’s disease. Zhongguo Yousheng yu Yichuan Zazhi. 1992;12(4): 105-107.
[28] Chen CY, Ding FZ, Yan CF, et al. Four cases of Huntington’s disease with ventrolateral nuclei of thalamus destruction treatment. Zhongguo Shenjing Jingshen Jibing Zazhi. 1992;18(4): 256.
[29] Hou FY, Li GQ. A family survey of Huntington’s disease. Jinzhou Yixueyuan Xuebao. 1993;14(2):82.
[30] Gao YJ, Cao XH, Yu ZB, et al. The clinic feature of a family with Huntington’s disease. Nao yu Shenjing Jibing Zazhi. 1994;2(3): 184.
[31] Dong QS. Huntington’s disease with haloperidol and γ- aminobutyric acid treatment. Zhongguo Yousheng yu Yichuan Zazhi. 1994;2(4):118.
[32] Huang YJ. Five cases of Huntington’s disease in one family. Zhongfeng yu Shenjing Jibing Zazhi. 1994;11(5):304.
[33] Yao XM, Shen SX, Wang JZ. Two cases with Huntington’s disease. Tianjin Yiyao. 1995;23(10):605-606.
[34] Fan XH, Zhang H. A case with Huntington’s disease associated with paranoid psychosis. Zhongguo Shenjing Jingshen Jibing Zazhi. 1995;21(5):318.
[35] Chu CH. Nine cases of Huntington’s disease in one family. Zhongfeng yu Shenjing Jibing Zazhi. 1995;12(2):108-109.
[36] Wang JY, Liu JG, Wang YF, et al. A case with Huntington’s disease. Taishan Yixueyuan Xuebao. 1995;16(1):61.
[37] Yong RH, Yang M. Two families of Huntington’s disease. Zhongguo Yousheng yu Yichuan Zazhi. 1995;3(6):109.
[38] Liu K, Xu L, Wang T. A case of Huntington’s disease and the family survey report. Zhongguo Zonghe Linchuang. 1996;12(5): 255-256.
[39] Shen ZZ, Bu XY, Qiu WQ, et al. A study of D_4S_(125)linked polymorphism associated with Huntington’s disease. Shanghai Yixue. 1996;19(1):5-7.
[40] Hou MJ. One family of Huntington’s disease. Zhonghua Yixue Yichuanxue Zazhi. 1997;14(3):189.
[41] Xia JM, Zhou Y. Ten cases of Huntington’s disease in two families. Anhui Yixue. 1997;18(3):64-65.
[42] Sun WH, Zhang CH. Eight cases of Huntington’s disease in one family. Linchuang Huicui. 1997;12(8):356-357.
[43] Fang XM. Two families of Huntington’s disease. Shiyong Yixue Zazhi. 1998;14(4):242.
[44] Liu WZ, Chen H, Pan H. The family survey of Huntington’s disease. Zhongguo Jiceng Yiyao. 1998;5(6):332.
[45] Zhang YJ. Clinic analysis and genetic counseling of 13 caess with Huntington’s disease. Linchuang Yixue. 1998;18(2):19-20.
[46] Yang XP, Xu YX. Five cases of Huntington’s disease in one family. Sichuan Yixue. 1998;19(4):354-355.
[47] Feng K, Lv XM, Liu J. A family report of Huntington’s disease. Zhongguo Meitan Gongye Yixue Zazhi. 1998;1(2):98.
[48] Gao ZZ, Yang XS, Tang BS. A survey of three families with Huntington’s disease. Zhongguo Yishi Zazhi. 1998;3(1):43-44.
[49] Zeng XP. Four cases of Huntington’s disease in one family. Zhonghua Yixue Yichuanxue Zazhi. 1998;15(4):217.
[50] Sun YC. Huntington’s disease. Tianjin Yiyao. 1998;26(1):38-39.
[51] Yang WG. Five cases of Huntington’s disease in one family. Linchuang Neike Zazhi. 1999;16(3):156.
[52] Wang GL. A child case with Huntington’s disease. Chengde Yixueyuan Xuebao. 1999;16(2):183-184.
[53] Liu B. Seven cases of Huntington’s disease in one family. Zhonghua Yixue Yichuanxue Zazhi. 1999;16(2):73.
[54] Zhang X. A case with mental disorder associated with Huntington’s disease. Linchuang Jingshen Yixue Zazhi. 2001; 11(5):285.
[55] Chen J, Zou T. A case of Huntington’s disease misdiagnosed as schizophrenia. Guiyang Yixueyuan Xuebao. 2001;26(6):557-560.
[56] Li W. Five cases of Huntington’s disease in one family. Nao yu Shenjing Jibing Zazhi. 2001;9(5):314.
[57] Dong QL, Cheng ZR. Analysis of seven cases of Huntington’s disease in one family. Linchuang Shenjingbing Xue Zazhi. 2001; 14(3):175.
[58] Fan HZ. A family survey of Huntington’s disease. Zhongguo Shengyu Jiankang Zazhi. 2001;12(4):156.
[59] Xu LS, Wang F. Fifteen cases of Huntington’s disease in one family. Xiandai Kangfu. 2001;5(1):92.
[60] Liu J, Han J, Wang J. Two families of Huntington’s disease. Zhongfeng yu Shenjing Jibing Zazhi. 2002;19(6):374.
[61] Deng BQ, Ding SJ, Zhang YW, et al. Eleven cases of Huntington’s disease in one family. Zhonghua Yixue Yichuanxue Zazhi. 2002; 19(2):137.
[62] Tian F. Pedigree analysis of a series of Huntington’s disease. Zhongguo Minzheng Yixue Zazhi. 2002;14(4):237-238.
[63] Ma HZ, Li LL, Wang YJ. The clinic features of five families with Huntington’s disease and literature review. Zhongguo Kangfu Lilun yu Shijian. 2003;9(7):434-436.
[64] Fang LQ. A case of mental disorder associated with Huntington’s disease. Linchuang Jingshen Yixue Zazhi. 2003;13(6):330.
[65] Zhao YH, Cong L, Pan Y, et al. IT15 gene analysis of two families with Huntington’s disease from Liaoning province. Zhongguo Yike Daxue Xuebao. 2003;32(4):355-357.
[66] Chen MB, Luo AL, Tian YK, et al. A case of Huntington’s disease undergoing emergency anesthesia. Zhonghua Mazuixue Zazhi. 2004;24(10):798.
[67] Tian Y. Three cases of Huntington’s disease in one family. Hanshao Jibing Zazhi. 2004;11(1):60.
[68] Dong WW, Zhang JT, Lang SY. The functional disorder analysis of a case with Huntington’s disease. Zhongguo Linchuang Kangfu. 2004;8(10):1919.
[69] Chen J, Zhang SY, Han CY, et al. Seven cases of Huntington’s disease in one family. Zhonghua Yixue Yichuanxue Zazhi. 2004;21(5):493.
[70] Wu JM. A family of Huntington’s disease. Zhonghua Yixue Yichuanxue Zazhi. 2004;21(2):178.
[71] Zhu BL, Tan YX, Ye HH, et al. Clinical features and gene study of five cases with Huntington’s disease in one family. Wenzhou Yixueyuan Xuebao. 2004;34(4):307-308.
[72] Guo LY, Li YX. A case of Huntington’s disease. Xiandai Yiyao Weisheng. 2005;21(13):1648.
[73] Zhang SY, Li Y, Guo HM. A family of Huntington’s disease. Zhonghua Yixue Yichuanxue Zazhi. 2006;23(5):535.
[74] Wang HM, Zhou QZ, Wu JM. A family of Huntington’s disease. Shenjing Jibing yu Jingshen Weisheng. 2006;6(5):383.
[75] Lin F, Chen ZX, Liu CF. Four cases of Huntington’s disease in one family. Zhonghua Yixue Yichuanxue Zazhi. 2006;23(4):486.
[76] Zhang BR, Song F, Yin XZ, et al. IT15 gene study of two families with Huntington’s disease. Yichuan. 2006;28(11):1345-1349.
[77] Shi ZL, Wang SY, Zhang YZ, et al. The clinical features analysis and gene diagnosis of a family with Huntington’s disease. Zhongguo Shengyu Jiankang Zazhi. 2006;17(02):99-100.
[78] Liu Y, Shen Y, Li H, et al. Intergeneration CAG expansion in a Wuhan juvenile-onset Huntington disease family. Neurosci Bull. 2007;23(4):198-202.
[79] Geng YC. Five cases of Huntington’s disease in one family. Shiyong Quanke Yixue. 2007;5(11):106.
[80] Xu W, Liu H, Huang R, et al. IT15 gene study in a family with Huntington’s disease. Zhongguo Xiandai Yixue Zazhi. 2008; 18(19):2832-2834.
[81] Yu J, Wu SW, Ma WY, et al. Two cases with Huntington’s disease. Wujing Yixue. 2008;19(8):756-757.
[82] Walker FO. Huntington's disease. Lancet. 2007;369(9557): 218-228.
[83] Quinn N, Schrag A. Huntington's disease and other choreas. J Neurol. 1998;245(11):709-716.
[84] Foroud T, Gray J, Ivashina J, et al. Differences in duration of Huntington's disease based on age at onset. J Neurol Neurosurg Psychiatry. 1999;66(1):52-56.
[85] Wang WZ. Neurology. Beijing: People’s Medical Publishing House. 2006.
[86] Margolis RL, Ross CA. Diagnosis of Huntington disease. Clin Chem. 2003;49(10):1726-1732.
[87] Nance MA. Clinical aspects of CAG repeat diseases. Brain Pathol. 1997;7(3):881-900.
[88] Duyao M, Ambrose C, Myers R, et al. Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat Genet. 1993;4(4):387-392.
[89] Stine OC, Pleasant N, Franz ML, et al. Correlation between the onset age of Huntington's disease and length of the trinucleotide repeat in IT-15. Hum Mol Genet. 1993;2(10):1547-1549.
[90] Nance MA, Myers RH. Juvenile onset Huntington's disease--clinical and research perspectives. Ment Retard Dev Disabil Res Rev. 2001;7(3):153-157.
[91] Mestre T, Ferreira J, Coelho MM, et al. Therapeutic interventions for symptomatic treatment in Huntington’s disease. Cochrane Database of Systematic Reviews. 2009(3). Art. No. CD006456. DOI:10.1002/14651858.CD006456.pub2.
[92] Adam OR, Jankovic J. Symptomatic treatment of Huntington disease. Neurotherapeutics. 2008;5(2):181-197.
[93] Baliko L, Csala B, Czopf J. Suicide in Hungarian Huntington's disease patients. Neuroepidemiology. 2004;23(5):258-260.
(Edited by Lou Y/Su LL/Song LP)