PDF(Pubmed)
Abstract：
Succinic semialdehyde dehydrogenase deficiency (SSADHD) (OMIM #271980) is a rare autosomal recessive metabolic disorder caused by pathogenic variants of ALDH5A1. Deficiency of SSADH results in accumulation of γ-aminobutyric acid (GABA) and other GABA-related metabolites. The clinical phenotype of SSADHD includes a broad spectrum of non-pathognomonic symptoms such as cognitive disabilities, communication and language deficits, movement disorders, epilepsy, sleep disturbances, attention problems, anxiety, and obsessive-compulsive traits. Current treatment options for SSADHD remain supportive, but there are ongoing attempts to develop targeted genetic therapies. This study aimed to create consensus guidelines for the diagnosis and management of SSADHD. Thirty relevant statements were initially addressed by a systematic literature review, resulting in different evidence levels of strength according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. The highest level of evidence (level A), based on randomized controlled trials, was unavailable for any of the statements. Based on cohort studies, Level B evidence was available for 12 (40%) of the statements. Thereupon, through a process following the Delphi Method and directed by the Appraisal of Guidelines for Research and Evaluation (AGREE II) criteria, expert opinion was sought, and members of an SSADHD Consensus Group evaluated all the statements. The group consisted of neurologists, epileptologists, neuropsychologists, neurophysiologists, metabolic disease specialists, clinical and biochemical geneticists, and laboratory scientists affiliated with 19 institutions from 11 countries who have clinical experience with SSADHD patients and have studied the disorder. Representatives from parent groups were also included in the Consensus Group. An analysis of the survey\'s results yielded 25 (83%) strong and 5 (17%) weak agreement strengths. These first-of-their-kind consensus guidelines intend to consolidate and unify the optimal care that can be provided to individuals with SSADHD.
摘要：
琥珀酸半醛脱氢酶缺乏症(SSADHD)(OMIM#271980)是由ALDH5A1的致病变体引起的一种罕见的常染色体隐性代谢紊乱。SSADH的缺乏导致γ-氨基丁酸(GABA)和其他GABA相关代谢物的积累。SSADHD的临床表型包括广泛的非病理症状，如认知障碍，沟通和语言障碍，运动障碍,癫痫,睡眠障碍,注意问题,焦虑,和强迫症特征。SSADHD的当前治疗选择仍然具有支持性，但仍在不断尝试开发靶向基因疗法。这项研究旨在为SSADHD的诊断和管理创建共识指南。最初通过系统的文献综述解决了30个相关陈述，根据建议评估的等级，产生不同的证据强度水平，发展,和评估（等级）标准。最高级别的证据（A级），基于随机对照试验，对任何语句都不可用。基于队列研究，B级证据可用于12（40％）的陈述。于是,通过遵循德尔菲法的过程，并由研究和评估指南(AGREEII)标准指导，寻求专家意见，SSADHD共识小组的成员评估了所有声明。这个小组由神经学家组成，癫痫学家,神经心理学家,神经生理学家,代谢疾病专家，临床和生化遗传学家，以及来自11个国家的19个机构的实验室科学家，他们具有SSADHD患者的临床经验并研究了该疾病。来自父母团体的代表也被纳入共识小组。对调查结果的分析得出25（83％）强和5（17％）弱协议强度。这些一流的共识指南旨在巩固和统一可以为SSADHD患者提供的最佳护理。
