[Blood 7-ketocholesterol level, clinical features and gene mutation analysis of 18 children with Niemann-Pick disease type C].

To investigate 7-ketocholesterol (7-KC) level in the blood, clinical features and gene mutation of Niemann-Pick disease type C (NPC).Eighteen patients diagnosed as NPC in Shanghai Xinhua Hospital seen from February 2013 to October 2014 were enrolled in this study. They included 13 males and 5 females and aged from 5 months to 21 years. The plasma 7-KC concentrations, clinical features and gene mutations of NPC patients were reviewed retrospectively.Fourteen NPC patients had neurological symptoms with the age of neurological onset from 1 year to 16 years. In seven cases the disease was early-infantile subtype, in 1 late-infantile subtype, in five juvenile subtype and in one adult subtype. The 7-KC value in the plasma of NPC patients was higher than the normal range, (348.5±168.7) μg/L in the early-infantile subtype, 150.6 μg/L in the late-infantile subtype, (145.0±46.3) μg/L in the juvenile subtype, and 32.0 μg/L in the adult subtype, respectively, additionally, four NPC patients had no observable neuropsychiatric disability when confirmed to be NPC by genetic testing, with the plasma 7-KC value (345.6±134.2) μg/L; 16 of 18 patients had splenomegaly or hepatosplenomegaly. Among 18 patients, 34 different mutations in the NPC1 gene were identified including 27 reported mutations, 1 novel small deletion 3609_3610delAC, five novel exonic point mutations, c. 3683T>C(M1228T), c. 3679A>T(R1227W), c. 1070C>T(S357L), c. 1456A>C(N486H) and c. 1142G>A(W381X) and 1 novel intronic mutation c. 881+ 3A>G.The 7-KC levels in the blood of patient was remarkably increased, and there was a tendency that 7-KC levels inversely correlated with the age of neurological onset. Most NPC patient had splenomegaly or hepatosplenomegaly. Among 18 patients, 34 different mutations in the NPC1 gene were identified including seven novel mutations, which enriched the gene mutation spectrum.