Department of Chemical Physiology & Biochemistry.
Knight Cardiovascular Institute, and Division of Endocrinology, Diabetes & Clinical Nutrition, Oregon Health & Science University, Portland, Oregon, USA.
Curr Opin Lipidol. 2021 Apr 1;32(2):123-131. doi: 10.1097/MOL.0000000000000740.
Cerebrotendinous xanthomatosis (CTX) is a rare genetic lipid storage disorder with highly pleomorphic clinical phenotype. Complications of this disease can be devastating and may include severe cognitive impairment and dementia in later stages. Disease progression can be prevented or stabilized by bile acid replacement therapy, although a subset of patients with advanced disease continue to deteriorate despite therapy.
Delayed diagnosis of CTX continues to impede effective treatment. A clinical diagnostic algorithm for CTX was developed that can decrease the age of diagnosis of CTX. The strategy of screening children with bilateral juvenile cataracts for CTX also improved diagnosis, as this group had a 500-fold higher-rate of CTX than the general population. Improved diagnosis of CTX is critical, as patients treated early in the course of the disease have significantly better outcomes compared with those treated later. More sensitive and specific biochemical testing for CTX has been developed that is potentially more informative than blood cholestanol to assess treatment efficacy and medication compliance in CTX.
Because we are recognizing more severe presentations of CTX in infants and children, and delayed diagnosis and treatment worsens the prognosis, CTX is an excellent candidate disorder for newborn screening using recently reported methods for newborn dried bloodspot analysis.
脑腱黄瘤病（CTX）是一种罕见的遗传性脂质贮积病，具有高度多样的临床表型。该疾病的并发症可能是毁灭性的，包括严重的认知障碍和后期的痴呆。尽管胆汁酸替代疗法可以预防或稳定疾病进展，但仍有一部分晚期疾病患者尽管接受了治疗仍继续恶化。
CTX 的延迟诊断继续阻碍有效的治疗。已经开发出一种用于 CTX 的临床诊断算法，可以降低 CTX 的诊断年龄。对双侧青少年白内障儿童进行 CTX 筛查的策略也改善了诊断，因为这一群体的 CTX 发病率比一般人群高 500 倍。改善 CTX 的诊断至关重要，因为在疾病早期治疗的患者与晚期治疗的患者相比，其预后显著改善。已经开发出更敏感和更特异的 CTX 生化检测方法，与血胆甾醇相比，该方法在评估 CTX 的治疗效果和药物依从性方面更具信息性。
由于我们在婴儿和儿童中发现了更严重的 CTX 表现，且延迟诊断和治疗会使预后恶化，因此使用最近报道的新生儿干血斑分析方法进行新生儿筛查，CTX 是一种极好的候选疾病。
