亞歷山大症

10.6666/ClinMed.201909_84(3).0104

林易徵；林詠萱；李宜中；廖翊筑

亞歷山大症（Alexander disease） ； 腦白質病變（leukoencephalopathy） ； GFAP基因（glial fibrillary acidic protein gene） ； 延髓徵候（bulbar symptoms）

臨床醫學月刊

84卷3期（2019 / 09 / 27）

639 - 642

繁體中文

亞歷山大症（Alexander disease）是一種體顯性遺傳的腦白質病變，典型的亞歷山大症發病於嬰兒期，病童會出現巨腦症、癲癇、發育遲緩，快速進展死亡。成人型亞歷山大症發病年齡變化很大，自青少年時期到五、六十歲發病均有可能，成人型亞歷山大症臨床特徵與嬰兒型不同，以延髓徵候（吞嚥困難和言語不清）及步態不穩為主要表現，部分病患會出現顎肌陣攣，出現此表徵強烈暗示為亞歷山大症。典型的亞歷山大症腦部核磁共振特徵為廣泛腦白質病變，包括大腦白質、基底核、視丘、腦幹都會受影響，以額葉白質病變最為顯著；腦室旁輪廓線狀T1WI高T2WI低訊號病灶也是此病特徵，可用來跟其他腦白質病變作區辨。成人型亞歷山大症腦部核磁共振特徵不同於典型嬰兒期發病患者，成人患者大腦白質變化輕微，小腦與腦幹白質病變較明顯，延腦與頸椎脊髓因明顯萎縮而呈現“蝌蚪狀＂為其特徵。亞歷山大症乃因GFAP基因上發生異型合子突變而致病，GFAP蛋白主要表現於神經系統的星狀膠細胞，GFAP突變蛋白會形成沉積物妨礙星狀膠細胞的有絲分裂、內質網與溶酶體正常構造，且影響到ATP釋放。基因治療包括反寡義核苷酸與CRISPR/Cas9技術在動物模型具治療效果，但應用於人體仍需進一步研究。

1. Alexander WS. Progressive fibrinoid degeneration of fibrillary astrocytes associated with mental retardation in ahydrocephalic infant. Brain 1949;72:373-81.
2. Brenner, M,Johnson, AB,Boespflug-Tanguy, O(2001).Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease.Nat Genet,27,117-120.
3. Hagemann, TL,Powers, B,Mazur, C(2018).Antisense suppression of glial fibrillary acidic protein as a treatment for Alexander disease.Ann Neurol,83,27-39.
4. Jones, JR,Kong, L,Hanna, MGt(2018).Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes.Cell Rep,25,947-958.
5. Namekawa, M,Takiyama, Y,Honda, J(2010).Adult-onset Alexander disease with typical "tadpole" brainstem atrophy and unusual bilateral basal ganglia involvement: a case report and review of the literature.BMC Neurol,10,21.
6. Pareyson, D,Fancellu, R,Mariotti, C(2008).Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature.Brain,131,2321-2331.
7. Prust, M,Wang, J,Morizono, H(2011).GFAP mutations, age at onset, and clinical subtypes in Alexander disease.Neurology,77,1287-1294.
8. van der Knaap, MS,Naidu, S,Breiter(2001).Alexander disease: diagnosis with MR imaging.AJNR Am J Neuroradiol,22,541-552.
9. Yoshida, T,Nakagawa, M(2012).Clinical aspects and pathology of Alexander disease, and morphological and functional alterationof astrocytes induced by GFAP mutation.Neuropathology,32,440-446.
10. Yoshida, T,Sasaki, M,Yoshida, M(2011).Nationwide survey of Alexander disease in Japan and proposed new guidelines for diagnosis.J Neurol,258,1998-2008.