Abstract
Niemann-Pick disease type C is an autosomal recessive lysosomal disorder clinically characterized by age-specific symptomatology with possible manifestation any time from neonatal age to late adulthood. Except for its neonatal form with cholestasis, respiratory failure and hepatosplenomegaly, the disease presents as a neurodegenerative disorder, frequently with splenomegaly.
Pathophysiology involves dysfunction of the late endosome/lysosome membraneous system with accumulation of unesterified cholesterol and glycosphingolipids due to mutations in the NPC1 and NPC2 genes coding the corresponding lysosomal proteins. Results of clinical examination must be confirmed by specific loading tests in cultivated fibroblasts and/or molecular genetic analysis of the concerned genes.
In the last years the disease is treated with a reversible glucosylceramide synthase inhibitor miglustat, potentially stabilizing its course. Recently, clinical testing of cyclodextrin has been initiated.
In the Czech Republic, comprehensive diagnostics is available at The Institute of Inherited Metabolic Disorders (67 confirmed patients including 42 Czechs).