Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Division of Child Neurology and Metabolic Medicine, Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.
Mol Genet Metab. 2022 Dec;137(4):436-444. doi: 10.1016/j.ymgme.2021.06.006. Epub 2021 Jun 24.
Early-onset forms of hereditary spastic paraplegia and inborn errors of metabolism that present with spastic diplegia are among the most common "mimics" of cerebral palsy. Early detection of these heterogenous genetic disorders can inform genetic counseling, anticipatory guidance, and improve outcomes, particularly where specific treatments exist. The diagnosis relies on clinical pattern recognition, biochemical testing, neuroimaging, and increasingly next-generation sequencing-based molecular testing. In this short review, we summarize the clinical and molecular understanding of: 1) childhood-onset and complex forms of hereditary spastic paraplegia (SPG5, SPG7, SPG11, SPG15, SPG35, SPG47, SPG48, SPG50, SPG51, SPG52) and, 2) the most common inborn errors of metabolism that present with phenotypes that resemble hereditary spastic paraplegia.
早发性遗传性痉挛性截瘫和以痉挛性双瘫为表现的先天性代谢错误是脑瘫最常见的“模拟病”之一。这些异质性遗传疾病的早期发现可以为遗传咨询、预期指导提供信息，并改善预后，特别是在存在特定治疗方法的情况下。该诊断依赖于临床模式识别、生化测试、神经影像学，以及越来越多的基于下一代测序的分子测试。在这篇简短的综述中，我们总结了以下疾病的临床和分子理解：1）儿童发病和复杂遗传性痉挛性截瘫（SPG5、SPG7、SPG11、SPG15、SPG35、SPG47、SPG48、SPG50、SPG51、SPG52），以及 2）以类似于遗传性痉挛性截瘫为表现的最常见先天性代谢错误。
