Department of Pediatric, Peking University First Hospital, Beijing 100034, China.
Gene. 2012 May 1;498(2):332-5. doi: 10.1016/j.gene.2012.01.026. Epub 2012 Feb 4.
Niemann-Pick disease type C (NP-C), caused by mutations of either NPC1 or NPC2 gene, is an inherited lysosomal lipid storage disorder that is difficult to be diagnosed and treated. NP-C is rarely reported in China and so far very few literatures are available for Chinese clinical workers. To better characterize this disease in China and improve genetic counseling, mutational analyses of NPC1 gene were carried out in 6 unrelated Chinese patients.
Clinical data of the probands from 2007 to 2010 were collected and analyzed. All exons of NPC1 were analyzed by direct sequencing.
The six cases, four males and two females, included three cases of late infantile subtype and three cases of juvenile subtype. Case one and case six had siblings who suffered from the same disease. The onset of clinical symptoms varied from three to ten years old, and they included progressive cognitive and language impairment, and motion retrogradation. All were caught by focal or generalized seizures from one to four years after the onset. Vertical supranuclear gaze palsy, dysarthria, dysphagia, internal rotation and adduction of bilateral hands and splenomegaly occurred gradually during the disease progression. Five patients had laughter-cataplexy. MRI indicated mild brain atrophy. Sea blue cells and Niemann-Pick cells were presented in bone marrow smears. Activity of acid sphingomyelinase was normal or only slightly lower than controls. Supporting and symptomatic treatments could improve some of the clinical signs. We identified 10 different NPC1 mutations were identified in 12/12 alleles, 3 of which are described for the first time. All mutations were missense mutations, which located throughout the gene with five clustering in the cysteine-rich luminal domain. Homozygous mutation of S865L correlated with a relatively severe juvenile neurological form.
NP-C is a rare autosomal recessive lysosomal storage disease that affects intellectual development of children, causing dementia, vegetative state and eventual death. The awareness of NP-C should be raised in the Chinese population. The typical clinical features of this disease include vertical supranuclear gaze palsy, seizures and cataplexy. Laboratory features include the presence of sea blue cells and Niemann-Pick cells in bone marrow smears. NPC1 mutation can be identified in most of these patients and most of them are missense mutations.
尼曼-皮克病 C 型（NP-C）由 NPC1 或 NPC2 基因突变引起，是一种遗传性溶酶体脂质贮积病，难以诊断和治疗。NP-C 在我国很少见，到目前为止，中国临床工作者可参考的文献也很少。为了更好地了解中国的这种疾病，并改善遗传咨询，对 6 名无亲缘关系的中国患者的 NPC1 基因进行了突变分析。
收集并分析了 2007 年至 2010 年患者的临床资料。通过直接测序分析 NPC1 的所有外显子。
6 例患者中，男 4 例，女 2 例，包括 3 例晚发性婴儿型和 3 例少年型。病例 1 和病例 6 有患有同种疾病的兄弟姐妹。临床症状的发病年龄从 3 岁到 10 岁不等，包括进行性认知和语言障碍以及运动倒退。发病后 1 至 4 年内，所有患者均出现局灶性或全身性癫痫发作。疾病进展过程中逐渐出现垂直性核上性眼球运动障碍、构音障碍、吞咽困难、双手内旋和内收以及脾肿大。5 例患者有大笑猝倒。MRI 提示轻度脑萎缩。骨髓涂片可见海蓝色细胞和尼曼-皮克细胞。酸性鞘磷脂酶的活性正常或仅略低于对照。支持和对症治疗可以改善一些临床体征。我们在 12/12 个等位基因中发现了 10 种不同的 NPC1 突变，其中 3 种是首次发现。所有突变均为错义突变，位于整个基因中，其中 5 个突变位于富含半胱氨酸的腔域。S865L 纯合突变与较为严重的少年型神经形式相关。
NP-C 是一种罕见的常染色体隐性溶酶体贮积病，影响儿童智力发育，导致痴呆、植物状态和最终死亡。应该提高中国人对 NP-C 的认识。这种疾病的典型临床特征包括垂直性核上性眼球运动障碍、癫痫发作和猝倒。实验室特征包括骨髓涂片可见海蓝色细胞和尼曼-皮克细胞。大多数患者都能检测到 NPC1 突变，大多数为错义突变。
