Niemann–Pick disease type C (NPC) is an autosomal recessive, neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. Mutations in these genes are associated with abnormal endosomal–lysosomal trafficking, resulting in the accumulation of tissue-specific lipids in lysosomes. We described sixteen patients with NPC diagnosed between the age of 1 month and 30 years at two tertiary care centers in Palestine. The clinical phenotype, brain magnetic resonance imaging (MRI), and molecular genetic analysis data were reviewed. The diagnosis was confirmed by molecular analysis in all patients. Fourteen out of sixteen patients were homozygous for the NPC1 p.G992W variant. Among them, most were categorized as having the late-infantile neurological form of disease onset. They predominantly manifested with early-onset visceral manifestations in the form of hepatosplenomegaly and prolonged neonatal jaundice, and late-onset neuropsychiatric manifestations in the form of vertical supranuclear gaze palsy (VSGP), ataxia, cognitive impairment and seizures. Brain MRI in 6 patients was normal in 5 or consistent with cerebellar hemisphere atrophy in 1 of them. Two other mutations were identified in the NPC1 gene, of which p.V845Cfs*24 was novel. Our results revealed phenotypic heterogeneity of NPC even within the same genotype, and add to the increasingly recognized evidence that cholestatic jaundice and hepatosplenomegaly during infancy, should alert the physician for the possibility of NPC. We reported a novel mutation in the NPC1 gene further expanding its genotype.

中文翻译：

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巴勒斯坦 C 型尼曼-匹克病：16 名患者的基因型和表型以及 NPC1 基因新突变的报告


C 型尼曼-皮克病 (NPC) 是一种常染色体隐性遗传的神经退行性疾病，由 NPC1 或 NPC2 基因突变引起。这些基因的突变与异常的内体-溶酶体运输有关，导致溶酶体中组织特异性脂质的积累。我们描述了在巴勒斯坦的两个三级护理中心诊断出的 16 名 NPC 患者，年龄在 1 个月至 30 岁之间。回顾了临床表型、脑磁共振成像（MRI）和分子遗传学分析数据。所有患者的诊断均通过分子分析得到证实。 16 名患者中有 14 名是 NPC1 p.G992W 变异纯合子。其中，大多数被归类为具有婴儿晚期神经系统疾病发病形式。他们主要表现为早发性内脏表现，如肝脾肿大和新生儿黄疸延长，以及迟发性神经精神表现，如垂直核上性凝视麻痹（VSGP）、共济失调、认知障碍和癫痫发作。 6 名患者中，5 名患者的脑 MRI 正常，或其中 1 名患者与小脑半球萎缩相符。在 NPC1 基因中还发现了另外两个突变，其中 p.V845Cfs*24 是新的。我们的结果揭示了即使在相同基因型内鼻咽癌的表型异质性，并增加了越来越多的证据表明婴儿期胆汁淤积性黄疸和肝脾肿大应提醒医生鼻咽癌的可能性。我们报道了 NPC1 基因的新突变，进一步扩展了其基因型。