Biallelic variants of 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) gene have been linked to neurodegenerative disorders ranging from severe neonatal encephalopathy to early-onset spastic paraplegia. We identified a novel homozygous variant, c.340G > T (p.Gly114Cys), in the HPDL gene in two siblings with autosomal recessive hereditary spastic paraplegia (HSP). Despite sharing the same likely pathogenic variant, the older sister had pure HSP, whereas her brother had severe and complicated HSP, accompanied by early-onset mental retardation and abnormalities in magnetic resonance imaging. Given the clinical heterogeneity and potential for treatable conditions in HPDL-related diseases, we emphasize the importance of genetic testing for the HPDL gene.

4-羟基苯丙酮酸双加氧酶样 ( HPDL ) 基因的双等位变体与从严重新生儿脑病到早发性痉挛性截瘫等神经退行性疾病有关。我们在患有常染色体隐性遗传性痉挛性截瘫 (HSP) 的两个兄弟姐妹的HPDL基因中发现了一个新的纯合变异 c.340G > T (p.Gly114Cys)。尽管具有相同的可能致病变异，但姐姐患有纯HSP，而她的哥哥则患有严重且复杂的HSP，并伴有早发性智力低下和磁共振成像异常。鉴于HPDL相关疾病的临床异质性和可治疗病症的潜力，我们强调HPDL基因基因检测的重要性。