亨丁頓病的臨床表徵與鑑別診斷

Clinical Manifestation and Differential Diagnosis of Huntington Disease

亨丁頓病（Huntington disease, HD），是一種體染色體顯性遺傳之神經退化性疾病，乃由HTT基因上之三核苷酸重複序列（CAG repeat）異常擴張所致。亨丁頓病的主要症狀，包括動作障礙、精神症狀及認知功能障礙，另外，也可見體重減輕，惡病質及異常的眼球運動等。平均的發病年齡是在35-44歲，但有5%的病人在21歲前發病，這類病人的臨床表徵與典型病人不同，稱為魏斯特法變異型（Westphal variant）。一般而言，愈早發病，症狀愈嚴重，疾病進展也愈快。診斷亨丁頓病，必須先排除可治療的疾病，如藥物或系統性疾病導致的次發性舞蹈症。有些病人雖然臨床症狀符合亨丁頓病，但約有1%的病患無法檢測出HTT基因上三核苷酸序列異常擴張之情形，這類疾病被統稱為亨丁頓病擬表型症候群（HD phenocopy syndromes），在這些病患，僅有部分病患可找到基因異常，如齒狀紅核蒼白球萎縮症（dentotorubral pallidoluysian atrophy, DRPLA）、亨丁頓病樣綜合徵（Huntington disease like, HD like 1-4；HDL1-4）、C9orf72六核苷酸重複擴張基因變異（C9orf72 hexanucleotide repeat expansion mutation）、ADCY5基因突變相關運動障礙（ADCY5-related dyskinesia）、神經棘狀紅血球症（neuroacanthocytosis）等。此類病人必須透過基因診斷才能確認，因此在檢測前必須接受遺傳諮詢及並做好健全的心理準備。

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by abnormal expansion of the CAG trinucleotide repeats on the HTT gene. The main symptoms of HD include movement disorders, psychiatric symptoms, and cognitive dysfunction. In addition, weight loss, cachexia, and abnormal eye movements are also commonly observed. The mean age of onset is 35-44 years old, but 5% of patients develop the symptoms before the age of 21. The clinical manifestations of such patients are different from typical patients, which is called Westphal variant. When the disease develops early, symptoms are more severe, and the disease progresses faster. The diagnosis of HD must first rule out treatable diseases, such as secondary chorea caused by drugs or systemic diseases. However, about 1% of patients cannot identify the abnormal expansion of the trinucleotide sequence on the HTT gene, who have clinical symptoms consistent with HD. These diseases are collectively referred to as Huntington’s disease phenocopy syndromes. Dentotorubral pallidoluysian atrophy (DRPLA), Huntington disease-like syndrome (Huntington disease-like syndrome) like (HD like 1-4; HDL1-4), C9orf72 hexanucleotide repeat expansion mutation, ADCY5-related dyskinesia, neuroacanthocytosis are among the differential diagnosis. Genetic counseling is required before the genetic testing.