Lathosterosis是一种罕见的常染色体隐性胆固醇生物合成疾病。它是由编码3-β-羟基类固醇-δ-5-去饱和酶(也称为甾醇-C5-去饱和酶或甾醇脱氢酶)的SC5D(甾醇C5-去饱和酶)基因中的缺陷引起的。文献中只描述了六个案例,但也有可能是一些病情较轻的患者漏诊。Lathosterolosis表现为小头畸形,双侧白内障,畸形,肢体异常,和发育迟缓/智力障碍。肝脏受累是可变的,可以从正常的肝功能检查到门静脉纤维化和肝硬化。通过证明SC5D基因中的特定突变和通过血浆甾醇分析以确认升高的甾醇水平来进行诊断。在这份报告中,我们描述了一个与发育迟缓/智力障碍相关的转胺炎女孩,面部畸形,肢体异常,和双侧白内障。Fibroscan显示严重的肝纤维化。血浆甾醇分析和外显子组测序证实了Lthosterolosis的诊断。辛伐他汀治疗可降低血浆甾醇水平,转氨酶的改善,和肝纤维化分级,提示患有这种疾病的儿童应积极治疗,以防止肝病进展。
Lathosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis. It is caused by defects in the SC5D (sterol C5-desaturase) gene which encodes for the 3-beta-hydroxysteroid-delta-5-desaturase (also called sterol-C5-desaturase or lathosterol dehydrogenase). Only six cases have been described in the literature, but it is possible that a number of patients with milder forms of the condition might have been missed.
Lathosterolosis manifests as microcephaly, bilateral cataracts, dysmorphism, limb anomalies, and developmental delay/intellectual disability. Liver involvement is variable and can range from normal liver function tests to portal fibrosis and cirrhosis. Diagnosis is made by demonstration of specific mutations in the SC5D gene and by plasma sterol analysis to confirm elevated lathosterol levels. In this report, we describe a girl with transaminitis in association with developmental delay/intellectual disability, facial dysmorphism, limb anomalies, and bilateral cataracts. Fibroscan showed severe liver fibrosis. Plasma sterol analysis and exome sequencing confirmed the diagnosis of
lathosterolosis. Simvastatin treatment resulted in lowering of plasma lathosterol levels, improvement in transaminitis, and liver fibrosis grade, suggesting that children with this condition should be actively treated in order to prevent progression of liver disease.