[Clinical features and gene mutation analysis of patients with Niemann-Pick disease type C].

Objective: To analyze the clinical manifestations, therapeutic efficacy, prognosis and characteristics of NPC1 mutation in Chinese patients with Niemann-Pick disease type C(NPC). Methods: Ten unrelated Chinese NPC patients were diagnosed by NPC1 mutation analysis from July 2013 to February 2017 in Beijing Tian Tan Hospital of Capital Medical University. Clinical data of 10 cases were analyzed retrospectively which included clinical manifestations, laboratory results and NPC1 gene mutation features, and a series of follow-up were carried out about therapeutic efficacy and prognosis. Results: Ten patients suffering from NPC included 5 males and 5 females, aged from 42 days to 14 years when they presented to Tian Tan Hospital. According to their age of neurological onset, 4 were in early infantile period, 2 in late infantile period, 2 in juvenile periods, and the other 2 cases in neonatal period. They all presented with splenomegaly, 5 of 10 accompanied with hepatomegaly. Two cases of neonatal subtype presented mainly with delayed neonatal cholestatic jaundice and hepatosplenomegaly, accompanied with decreased muscle tone and slight psychomotor retardation. The other 8 cases presented with severe neurological involvement, such as progressive encephalopathy, ataxia and language impairment, 4 with dystonia, 3 with decreased muscle tension, 5 with vertical supranuclear gaze palsy, 5 with gelastic cataplexy, and 4 with epilepsy. Eight of 9 cases presented with foam cells in their bone marrow. Head MRI showed diffuse cerebral atrophy in 8 cases, thin corpus callosum in 2 cases, and brain white matter abnormal signals in 2 cases. Among 10 cases, 18 different mutations of NPC1 allelic genes were identified including 11 reported mutations, 3 novel missense mutations: c. 3683T>C (p.Met1128Thr), c.1926G>C (p.Met642Iie) and c. 3006C>G (p.Phe1002Leu), 2 novel nonsense mutation: c. 1142G>A(p.Trp381Ter ) and c. 3229C>T(p.Arg1077Ter), 1 novel minimal deletion mutation: c. 1385-1386del, and 1 novel intron mutation: c. 1757+ 5G>A. In 5 cases, the symptom of gelastic cataplexy was alleviated by imipramine, and the convulsion was relieved by valproate in 2 cases, by carbamazepine in 1 case at the beginning of seizure. During the 25 (3-66) months of follow-up, 4 cases died, the others' neurological symptoms were deteriorated progressively. Conclusions: The NPC1 gene mutation were high heterozygous in this group, and 7 novel mutations enriched the gene mutation spectrum of NPC1. The neurological manifestations were complicated in patients with NPC, and the symptomatology would be different according to their onset age of neurological symptoms. There might be effective symptomatic treatment for gelastic cataplexy by imipramine and for convulsion by valproate or carbamazepine.