Fusco Carlo, Russo Angelo, Galla Daniela, Hladnik Uros, Frattini Daniele, Giustina Elvio Della
1Pediatric Neurology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
J Child Neurol. 2013 Dec;28(12):1694-7. doi: 10.1177/0883073812462765. Epub 2012 Oct 30.
Niemann-Pick type C is an autosomal recessive lipid storage disease caused by mutations in the NPC1 or NPC2 gene. In childhood-onset Niemann-Pick type C, the usual course is slowly progressive, with normal cerebral magnetic resonance at onset. Here the authors present the case of a patient carrying 2 compound heterozygous NPC1 mutations: the known nonsense mutation (p.Trp833X) in exon 16 and a novel missense mutation (p.Ile609Phe) in exon 12. At onset, the patient presented ataxia, cognitive decline, and epilepsy, with early cerebral atrophy and marked cerebellar vermis atrophy. The course of the disease was rapid, and the patient died within 1-2 years of onset. A possible phenotype-genotype correlation is discussed. This case further expands the clinical spectrum and the genetic heterogeneity of Niemann-Pick type C due to NPC1 mutations.
尼曼-匹克C型是一种常染色体隐性脂质贮积病，由NPC1或NPC2基因突变引起。在儿童期起病的尼曼-匹克C型中，通常病程呈缓慢进展，起病时脑磁共振成像正常。本文作者报告了1例携带2种复合杂合NPC1突变的患者：外显子16中已知的无义突变（p.Trp833X）和外显子12中的一种新的错义突变（p.Ile609Phe）。起病时，患者出现共济失调、认知衰退和癫痫，伴有早期脑萎缩和明显的小脑蚓部萎缩。疾病病程进展迅速，患者在起病后1至2年内死亡。文中讨论了一种可能的表型-基因型相关性。该病例进一步扩展了由NPC1突变导致的尼曼-匹克C型的临床谱和基因异质性。
