Sepiapterin reductase deficiency: A Treatable Mimic of Cerebral Palsy
Sepiapterin reductase deficiency: A Treatable Mimic of Cerebral Palsy
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DOI：
10.1002/ana.22685
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发表时间：
2012-04-01
影响因子：
11.2
通讯作者：
Blau, Nenad
中科院分区：
文献类型：
--
作者：
Friedman, Jennifer;Roze, Emmanuel;Blau, Nenad
目的：sepapterin reductase deficiency （SRD）是一种未被充分认识的左旋多巴反应性障碍。我们描述临床，生化和分子的发现在一个队列的患者与这种可治疗的条件。我们的目标是提高对表型和可用的诊断和治疗策略的认识，以减少延误诊断或误诊，优化管理，并提高对病理生理机制的理解。方法：从23个国际医疗中心鉴定43例SRD患者。表型和治疗反应通过使用详细的标准化仪器的图表回顾和对无法获得记录的病例的文献回顾来评估。结果：在大多数情况下，运动和语言迟缓，轴性张力低下，肌张力障碍，无力，眼危象和睡眠益处的昼夜波动症状在婴儿期或儿童期变得明显。平均发病年龄为7个月，诊断延迟9.1年。脑瘫（CP）的误诊是常见的。大多数患者从左旋多巴/卡比多巴中获益显著，通常在添加5-羟色氨酸后进一步改善。脑脊液的表现是独特的。诊断是通过突变分析和/或酶活性测定培养成纤维细胞。解释：SRD常见的临床表现，除了眼部危象和昼夜波动外，是非特异性的，类似于肌张力低下或肌张力障碍的CP。经过治疗，病人通常会显著好转。因此，我们建议不仅在左旋多巴反应性运动障碍患者中考虑SRD，而且在发育迟缓伴轴向肌紧拉症患者和不明原因或不典型推定CP患者中也考虑SRD。脑脊液生化检查是首选的初步调查方法。建议早期诊断和治疗以防止持续的脑功能障碍。神经网络学报2012；71: 520 - 530
Objective: Sepiapterin reductase deficiency (SRD) is an under-recognized levodopa-responsive disorder. We describe clinical, biochemical, and molecular findings in a cohort of patients with this treatable condition. We aim to improve awareness of the phenotype and available diagnostic and therapeutic strategies to reduce delayed diagnosis or misdiagnosis, optimize management, and improve understanding of pathophysiologic mechanisms.Methods: Forty-three individuals with SRD were identified from 23 international medical centers. The phenotype and treatment response were assessed by chart review using a detailed standardized instrument and by literature review for cases for which records were unavailable.Results: In most cases, motor and language delays, axial hypotonia, dystonia, weakness, oculogyric crises, and diurnal fluctuation of symptoms with sleep benefit become evident in infancy or childhood. Average age of onset is 7 months, with delay to diagnosis of 9.1 years. Misdiagnoses of cerebral palsy (CP) are common. Most patients benefit dramatically from levodopa/carbidopa, often with further improvement with the addition of 5-hydroxytryptophan. Cerebrospinal fluid findings are distinctive. Diagnosis is confirmed by mutation analysis and/or enzyme activity measurement in cultured fibroblasts.Interpretation: Common, clinical findings of SRD, aside from oculogyric crises and diurnal fluctuation, are nonspecific and mimic CP with hypotonia or dystonia. Patients usually improve dramatically with treatment. Consequently, we recommend consideration of SRD not only in patients with levodopa-responsive motor disorders, but also in patients with developmental delays with axial hypotonia, and patients with unexplained or atypical presumed CP. Biochemical investigation of cerebrospinal fluid is the preferred method of initial investigation. Early diagnosis and treatment are recommended to prevent ongoing brain dysfunction. ANN NEUROL 2012; 71: 520-530