ABSTRACT
Objective To established a diagnostic methods to idenfity Niemann-Pick disease type C (NPC) in China. Methods Two patients aged 5 and 20 years respectively who presented progressive neurologic regression and splenomegaly were subjected to filipin staining of cultured skin fibroblasts and genetic analyses of NPC1 gene. Results Although there were differences in onset ages and clinical presentations, filipin staining of the cultured skin fibroblasts confirmed the clinical diagnosis of NPC, showing an intense punctate pattern of fluorescence concentrating around the nuclei, consistent with the accumulation of unesterified cholesterol in NPC cells. Genetic sequence analysis further verified the results of filipin staining. The case 1 was compound heterozygous for M1142T(3425T＞C),R1186H(3557T＞C)and case 2 for Q88H(264G＞T),469_470insGT.The latter 2 mutations were novel, and the possibility of polymorphisms was not supposed by analyzing 134 DNA samples obtained form normal controls. Conclusions Filipin stainning of the cultured skin fibroblasts is a reliable method to clinically diagnose NPC with a sensitivity. Genetic diagnose should be performed where genetic analysis is allowed.