Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Curr Opin Lipidol. 2013 Aug;24(4):283-7. doi: 10.1097/MOL.0b013e328362df13.
Cerebrotendinous xanthomatosis (CTX) is a rare neurological disease characterized by accumulation of cholesterol and cholestanol in brain and tendons caused by a mutation in the sterol 27-hydroxylase gene (CYP27A1). The mechanism behind the accumulation of cholestanol in the brain was recently clarified and a role of 27-hydroxycholesterol as a regulator of brain cholesterol homeostasis has been established.
There is a significant flux of the bile acid precursor 7α-hydroxy-4-cholesten-3-one across the blood-brain barrier in cy27-/- mice with its subsequent conversion into cholestanol. CTX patients with white matter lesions and vacuolation are described. CYP27A1 was identified as a candidate gene for sporadic amyotrophic lateral sclerosis (ALS).
The mechanism behind accumulation of cholestanol in brain and tendons of patients with CTX has been clarified but it is not known why this accumulation is associated with parallel accumulation of cholesterol and formation of xanthomas. Further studies are needed to understand why some patients with CTX develop white matter lesions in the brain. In view of the fact that CTX can present with upper motor neuronal signs it is interesting that CYP27 has been shown to be a candidate gene for sporadic ALS.
脑腱黄瘤病（CTX）是一种罕见的神经疾病，其特征是由于胆固醇 27-羟化酶基因（CYP27A1）突变导致脑和肌腱中胆固醇和植物固醇积累。最近阐明了脑内植物固醇积累的机制，并确立了 27-羟胆固醇作为脑胆固醇稳态调节剂的作用。
在 cy27-/- 小鼠中，存在胆汁酸前体 7α-羟基-4-胆甾-3-酮穿过血脑屏障的显著通量，随后转化为植物固醇。描述了伴有白质病变和空泡形成的 CTX 患者。CYP27A1 被确定为散发性肌萎缩侧索硬化症（ALS）的候选基因。
阐明了 CTX 患者脑和肌腱中植物固醇积累的机制，但尚不清楚为什么这种积累与胆固醇的平行积累和黄瘤的形成有关。需要进一步研究以了解为什么一些 CTX 患者的大脑会出现白质病变。鉴于 CTX 可表现为上运动神经元体征，有趣的是，CYP27 已被证明是散发性 ALS 的候选基因。
