Sjogren-Larsson Syndrome: a Longitudinal Study of Natural History

干燥-拉尔森综合症：自然历史的纵向研究

• 批准号: 8936524
• 负责人: WILLIAM B. RIZZO
• 金额: $ 18万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8936524
• 关键词: Age; Biochemical; Biochemical Markers; Biological Markers; Biopsy; Blood; Clinical; Clinical Trials; Cognitive; Cutaneous; Data; Databases; Defect; Dermatologic; Development; Disease; Disease Progression; Doctor of Medicine; Electroencephalography; Enrollment; Erythrocytes; Evaluation; Evaluation Studies; Exhibits; Future; Gene Expression; Goals; Hereditary Disease; Ichthyoses; Intellectual functioning disability; Knowledge; Laboratories; Lipids; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Medical center; Metabolic; Methods; Monitor; Myelin; Natural History; Nebraska; Neurodevelopmental Disability; Neurologic; Optical Coherence Tomography; Pathogenesis; Patients; Plasma; Principal Investigator; Prospective Studies; Proteins; Proteomics; Rare Diseases; Recruitment Activity; Registries; Research; Research Personnel; Seizures; Severities; Severity of illness; Sjogren-Larsson Syndrome; Skin; Sterols; Symptoms; Testing; Therapy Clinical Trials; Universities; Urine; Variant; base; biobank; clinical phenotype; cohort; disability; disease phenotype; disease-causing mutation; disorder of macula of retina; in vivo; isoprenoid; keratinocyte; lipid metabolism; long-chain-aldehyde dehydrogenase; neuropsychiatry; oxidation; patient registry

Project 2 Sjogren-Larsson syndrome (SLS) is a rare genetic disease caused by mutations in ALDH3A2 that encodes fatty aldehyde dehydrogenase (FALDH) and results in defective isoprenol oxidation and abnormal lipid metabolism. Patients typically exhibit ichthyosis, intellectual disability, spasticity, seizures and a distinctive maculopathy. Although the disease was described more than 50 years ago, longitudinal natural history studies of SLS are non-existent and the clinical spectrum of this rare disease is not yet established. The pathogenic mechanisms of the disease remain unclear and no specific pathogenesis-based therapy exists. Moreover, biomarkers that correlate with disease severity or progression have not been established. We will conduct a longitudinal natural history study of SLS to define long term changes in clinical phenotype and search for biomarkers that correlate with symptom severity and clinical disease. Subjects of all ages will be enrolled. Patients will receive detailed clinical exams documenting their neurologic, dermatologic and cognitive disabilities. Neurologic, ophthalmologic, dermatologic, and neuropsychiatric changes will be documented with MRI/MRS, EEG, optical coherence tomography, cutaneous photographs and neuropsychiatric testing. Blood, urine, skin and cutaneous scales will be investigated for potential biomarkers using lipidomics, proteomics and gene expression methods. Clinical and laboratory data will be correlated to identify useful biomarkers that predict disease severity and progression. A SLS Biorepository of blood (plasma, erythrocytes), urine, skin biopsies and keratinocyte cultures will be established for sharing with STAIR and outside investigators. When this study is completed, we expect to have a thorough knowledge of the natural history and clinical variation of SLS. The biomarkers that will be discovered from this research should serve as validated measures of disease for monitoring therapeutic trials.

项目 2 干燥综合征 (SLS) 是一种罕见的遗传性疾病，由编码脂肪醛脱氢酶 (FALDH) 的 ALDH3A2 突变引起，并导致异戊二烯氧化缺陷和脂质代谢异常。患者通常表现出鱼鳞病、智力障碍、痉挛、癫痫发作和独特的黄斑病。尽管这种疾病在 50 多年前就已被描述，但 SLS 的纵向自然史研究还不存在，而且这种罕见疾病的临床谱尚未确定。该疾病的发病机制尚不清楚，并且不存在基于具体发病机制的治疗方法。此外，与疾病严重程度或进展相关的生物标志物尚未确定。我们将对 SLS 进行纵向自然史研究，以确定临床表型的长期变化，并寻找与症状严重程度和临床疾病相关的生物标志物。所有年龄段的受试者都将被招募。患者将接受详细的临床检查，记录他们的神经、皮肤和认知障碍。神经病学、眼科、皮肤病学和神经精神学变化将通过 MRI/MRS、EEG、光学相干断层扫描、皮肤照片和神经精神学测试进行记录。将使用脂质组学、蛋白质组学和基因表达方法研究血液、尿液、皮肤和皮肤鳞片的潜在生物标志物。将临床和实验室数据关联起来，以确定预测疾病严重程度和进展的有用生物标志物。将建立血液（血浆、红细胞）、尿液、皮肤活检和角质形成细胞培养物的 SLS 生物储存库，以便与 STAIR 和外部研究人员共享。当这项研究完成后，我们希望对 SLS 的自然史和临床变异有全面的了解。从这项研究中发现的生物标志物应作为疾病的有效测量指标，用于监测治疗试验。