Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management.
Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management.
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DOI：
10.1186/s13023-014-0179-4
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发表时间：
2014-11-26
影响因子：
3.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Nie S;Chen G;Cao X;Zhang Y
脑腱黄瘤病（CTX）OMIM#213700是一种罕见的常染色体隐性脂质储存疾病，由CYP 27 A1基因突变引起;该基因编码线粒体酶固醇27-羟化酶，参与胆汁酸合成。CYP 27 A1基因位于染色体2 q33-qter，包含9个外显子。CYP 27 A1突变导致胆汁酸合成减少，胆甾烷醇过量产生，并导致胆甾烷醇在组织中蓄积。目前对CTX的患病率没有共识，一种估计是全世界<5/100，000。在白人中，仅由CYP 27 A1突变R362 C引起的CTX患病率约为1/50，000。CTX患者在诊断时的平均年龄为35岁，诊断延迟16年。临床体征和症状包括成人发作的进行性神经功能障碍（即，共济失调、肌张力障碍、痴呆、癫痫、精神障碍、周围神经病和肌病）和过早的非神经学表现（即，肌腱黄瘤、儿童期发作的白内障、运动后发作的腹泻、过早的动脉粥样硬化、骨质疏松症和呼吸功能不全）。青少年白内障、进行性神经功能障碍和轻度肺功能不全是将CTX与其他脂质储存疾病（包括家族性β脂蛋白异常血症、纯合子家族性高胆固醇血症和谷甾醇血症）区分开来的独特症状，所有这些疾病也可能与黄色瘤和心血管疾病一起出现。脑磁共振成像（MRI）显示双侧小脑齿状核病变和轻度白色病变。经典的症状和体征，即血清和尿液中胆甾烷醇和胆汁醇水平升高，脑MRI和CYP 27 A1基因突变证实了CTX的诊断。早期诊断和鹅去氧胆酸（750 mg/d）的长期治疗可改善神经系统症状，并有助于改善预后。
Cerebrotendinous xanthomatosis (CTX) OMIM#213700 is a rare autosomal-recessive lipid storage disease caused by mutations in the CYP27A1 gene; this gene codes for the mitochondrial enzyme sterol 27-hydroxylase, which is involved in bile acid synthesis. The CYP27A1 gene is located on chromosome 2q33-qter and contains nine exons. A CYP27A1 mutation leads to decreased synthesis of bile acid, excess production of cholestanol, and consequent accumulation of cholestanol in tissues. Currently there is no consensus on the prevalence of CTX, one estimate being <5/100,000 worldwide. The prevalence of CTX due to the CYP27A1 mutation R362C alone is approximately 1/50,000 in Caucasians. Patients with CTX have an average age of 35 years at the time of diagnosis and a diagnostic delay of 16 years. Clinical signs and symptoms include adult-onset progressive neurological dysfunction (i.e., ataxia, dystonia, dementia, epilepsy, psychiatric disorders,peripheral neuropathy, and myopathy) and premature non-neurologic manifestations (i.e., tendon xanthomas, childhood-onset cataracts, infantile-onset diarrhea, premature atherosclerosis, osteoporosis, and respiratory insufficiency). Juvenile cataracts, progressive neurologic dysfunction, and mild pulmonary insufficiency are unique symptoms that distinguish CTX from other lipid storage disorders including familial dysbetalipoproteinemia, homozygous familial hypercholesterolemia, and sitosterolemia, all of which might also present with xanthomas and cardiovascular diseases. Brain magnetic resonance imaging (MRI) shows bilateral lesions in the dentate nucleus of the cerebellum and mild white matter lesions. The classical symptoms and signs, namely elevated levels of cholestanol and bile alcohols in serum and urine, brain MRI, and the mutation in the CYP27A1 gene confirm the diagnosis of CTX. Early diagnosis and long-term treatment with chenodeoxycholic acid (750 mg/d) improve neurological symptoms and contribute to a better prognosis.
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