Fabry Disease
Recessive?
Dr Wang reported that ss many as 76 percent of carrier women experience symptoms of the disease. So he suggested that Fabry disease should not be considered an X-linked recessive disorder and that heterozygous Fabry women should not be called carriers because they experience significant life-threatening conditions requiring medical treatment and intervention.
Fabry Disease
More than 250 kinds of GLA DNA mutations Majority of them are point mutations
Fabry Disease Frequency?
1/55,000 male JAMA. 1999; 281: 249-54 1/3,100 male Am. J. Hum. Genet. 2006; 79: 31-40, Based on this result, Fabry became the most common lysosomal storage disorder.
Classification by Clinical Features
Typical Atypical, Cardiac variant
பைடு நூலகம்
Typical disease course in a classically affected male hemizygote with Fabry disease.
2014 2013 2012 2011 2010
/statistics/entry
“Soon there will be no disease called breast cancer,” says Draghia-Akli. Instead, the catch-all term will be replaced
罕见病
---从溶酶体病说起
故事从一个罕见病说起…….
溶酶体贮积症 LSDs Lysosomal Storage Disorders
由于基因突变或染色体畸变导 致的，溶酶体发挥其正常功能 所需的一种或多种酶类分子， 或调控分子，功能减弱或丧失 引起的疾病成为溶酶体病。
由于该类疾病常常可见相应的 底物或／和其衍生物在溶酶体 内大量累积，因此通常称之为 溶酶体贮积症。在遗传病分类 上属于遗传代谢性疾病。
罕见病是病种细分后的必然结果
疾病的分类和命名 现代医学的发展必然使得疾病的种类越来越多 每种疾病所占的比例也就越来越小 小到足以称之为“罕见病”。
/s/blog_698a79070100pgc8.html
面对“罕见病时代” 我们准备好了吗？
罕见病有多少种？
Clathrin-coated lysosome
贮积物的性质和形态可以作为鉴别诊断的依据
Neuronal Ceroid Lipofuscinosis (NCL)
NCL1
NCL2
NCL3
溶酶体贮积症分类
Mucopolysaccaridoses 粘多糖贮积病 Glycoproteinoses 糖蛋白贮积病 Glycogen storage 糖原贮积病 Sphingolipidoses 神经鞘脂贮积病 Lipid storage disorders 脂质贮积病 Multiple enzyme defects 多酶缺陷 Transport defects 转运缺陷
Wang et al. Genet. Med. 9: 34-45, 2007.
肥厚型心肌病患者中 3-6% 为Fabry
肾透析病患者中 0.2% 为Fabry
18-55岁脑中风病人中 2 - 5% 为Fabry
常见的病，罕见的病因。
罕见病的定义
罕见病 Rare Diseases
“A disease is rare if fewer than 200,000 people in the United States have it. There are close to 7,000 rare diseases and about 25 million people in the U.S. have one. Many rare diseases are caused by changes in genes and are called genetic diseases.”
From Medline：/medlineplus/rarediseases.html
总发病率：~ 8.3％ 发病率：200,000/300,000,000 < 1/1500的为罕见病。 平均发病率：25,000,000/7,000*300,000,000 = 1/120,000
Fabry Disease
Dr Johannes Fabry Dr William Anderson
Anderson-Fabry Disease
Fabry Disease
Angiokeratoma Corporis Diffusum 弥漫性躯体性血管角化瘤
Fabry Disease
X-linked Lysosomal Storage Disorder Deficiency of α- galactosidase A (GLA) Accumulation of globotriaosylceramide (Gb3)
by “a large number of rare diseases, each of which