Department of Neurology, Canisius Wilhelmina Hospital, PO Box 9015, 6500GS, Nijmegen, The Netherlands.
Child and Adolescent Psychiatry Department, University Hospital of Nantes, Nantes, France.
J Inherit Metab Dis. 2018 Jul;41(4):641-646. doi: 10.1007/s10545-017-0086-7. Epub 2017 Sep 11.
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism (IEM) due to mutations in the CYP27A1 gene. The clinical picture ranges from being nearly asymptomatic in early childhood, up to severe disability at adult age. Infantile-onset diarrhea and juvenile-onset cataract are the earliest symptoms in childhood. In the current study, we evaluated the presence of autism spectrum disorder (ASD) in a large cohort of CTX patients.
We performed a retrospective patient file study in 77 genetically confirmed Dutch CTX patients to determine the frequency of ASD. In addition, we compared plasma cholestanol levels in CTX patients with and without a diagnosis of ASD and tried to establish a relation between CYP27A1 genotype and ASD.
In our CTX cohort, 10 patients (13%; nine pediatric and one adult) with ASD were identified. At the time of diagnosis of ASD, most patients only exhibited symptoms of diarrhea and/or intellectual disability without signs of cataract or neurological symptoms. No correlation was found between the presence of ASD and the level of cholestanol or CYP27A1 genotype. The behavioral problems stabilized or improved after treatment initiation with chenodeoxycholic acid (CDCA) in all pediatric patients.
We conclude that ASD is an early and probably underestimated frequent feature in CTX. Metabolic screening for CTX should be performed in patients with ASD when accompanied by diarrhea, intellectual disability, juvenile cataract, and/or neurological involvement. Early recognition allows for earlier initiation of specific treatment and will improve clinical outcome. Our results add CTX to the list of treatable IEMs associated with ASD.
脑腱黄瘤病（CTX）是一种常染色体隐性遗传性代谢缺陷病（IEM），由 CYP27A1 基因突变引起。临床表现从儿童早期几乎无症状到成年后严重残疾不等。婴儿期起病的腹泻和青少年期起病的白内障是儿童期最早的症状。在本研究中，我们评估了一大群 CTX 患者中自闭症谱系障碍（ASD）的存在。
我们对 77 名经基因证实的荷兰 CTX 患者进行了回顾性患者病历研究，以确定 ASD 的频率。此外，我们比较了 CTX 患者和无 ASD 患者的血浆胆甾烷醇水平，并试图建立 CYP27A1 基因型与 ASD 之间的关系。
在我们的 CTX 队列中，确定了 10 名（13%；9 名儿科和 1 名成人）患有 ASD 的患者。在 ASD 诊断时，大多数患者仅表现出腹泻和/或智力障碍的症状，没有白内障或神经系统症状的迹象。ASD 的存在与胆甾烷醇水平或 CYP27A1 基因型之间没有相关性。在所有儿科患者中，开始用鹅脱氧胆酸（CDCA）治疗后，行为问题稳定或改善。
我们得出结论，ASD 是 CTX 的一个早期且可能被低估的常见特征。当 ASD 伴有腹泻、智力障碍、青少年白内障和/或神经系统受累时，应进行 CTX 的代谢筛查。早期识别可更早开始特定治疗，并改善临床结果。我们的结果将 CTX 添加到与 ASD 相关的可治疗 IEM 列表中。
