Chanarin-Dorfman syndrome

Background: Chanarin-Dorfman syndrome is a rare autosomal recessive disease characterized by accumulation of triglycerides in cells from multiple organs. Its exact prognosis is not well known because of a lack of case series. It is often treated using oral retinoid but risk-benefit ratio of this drug has not been properly studied. Objective: To improve the management of patients by bringing new clinical, molecular and therapeutic data. Methods: Large retrospective multi-center observational research study performed by international expert centers combined with a comprehensive literature search. Results: A total of 38 patients were included. Molecular analysis revealed 19 different mutations including 7 unreported previously. Clinical data and follow-up data were available for 31 patients (median follow-up: 8 years (range: 0 – 38 years)). Skin anomalies (mild to severe ichthyosis) were present in all patients. Liver abnormalities (including 3 cirrhosis) were the most frequent extracutaneous change (28 patients). A total of 17 of the 31 patients received oral retinoids during a median duration of 7.9 years (range: 0.5 – 19.1 years) and one had cirrhosis diagnosed during treatment. Limitations: Retrospective design. Difficulty of comparison with the previously published data because of a lack of standardized reporting outcomes. Conclusion: The risk-benefit ratio appears to be in favor of the use of oral retinoids in cases with severe cutaneous disease.背景：查纳林-多夫曼综合征（Chanarin-Dorfman Syndrome）是一种罕见的常染色体隐性遗传病，特征为多器官细胞内甘油三酯蓄积。由于缺乏病例系列研究，其确切预后尚不明确。该病常采用口服维A酸类药物治疗，但该药物的风险获益比尚未得到充分研究。 目标：旨在获取新的临床、分子及治疗相关数据，以改善患者的管理方案。 方法：本研究为大型回顾性多中心观察性研究，由国际专家中心开展，并结合了全面的文献检索。 结果：本研究共纳入38例患者。分子分析检出19种不同的突变，其中7种为此前未报道过的新突变。31例患者拥有完整的临床数据及随访数据（中位随访时间：8年，范围：0~38年）。所有患者均存在皮肤异常（轻度至重度鱼鳞病）。肝脏异常（含3例肝硬化）是最常见的皮肤外受累表现（共28例）。31例患者中共有17例接受了口服维A酸类药物治疗，中位治疗时长为7.9年（范围：0.5~19.1年），其中1例在治疗期间被诊断为肝硬化。 局限性：本研究为回顾性设计；由于缺乏标准化的结局报告，与既往已发表研究的数据对比存在难度。 结论：对于存在重度皮肤受累的患者，口服维A酸类药物的风险获益比似乎支持其临床应用。