Newborn presentation of Niemann–Pick disease type C – Difficulties and limitations of diagnostic methods

Abstract

Abstract Niemann-Pick disease type C (NPC) is a neurodegenerative, lysosomal lipid storage disorder with a broad clinical heterogeneity. We present a newborn with congenital NPC despite normal results of pregnancy ultrasounds but with axial hypotonia and hepatosplenomegaly accompanied by elevated liver transaminases with severe bleeding diathesis within the first week of life. Light microscope examination of the liver biopsy specimens missed the proper diagnosis. Increasing results of double measurement of serum chitotriosidase activity were suggestive for storage process intensivity and subsequently the filipin test had been done. The first results were inconclusive requiring a longer time of culturing skin fibroblasts with lipoprotein deficient serum (Vanier protocol). Finally, a typical staining profile was demonstrated. Molecular analysis of NPC1 and NPC2 genes revealed the patient to be a compound heterozygote for mutations c.1920delG and c.2196dupT in the NPC1 gene confirming the diagnosis of Niemann-Pick disease type C. It is essential that each of the diagnostic tests for NPC has its own limitations contributing to a delay in the definite diagnosis.