A rare case of Niemann–Pick disease type C without neurological involvement in a 66-year-old patient

• Main Authors: C.R. Greenberg, J.G. Barnes, S. Kogan, L.E. Seargeant
• Format: Article
• Language: English
• Published: Elsevier 2015-06-01
• Series: Molecular Genetics and Metabolism Reports
• Subjects: Niemann–Pick disease type C (NP-C); Splenomegaly; Organomegaly; Asymptomatic
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214426915000117

The case of a 66 year-old female — the oldest known living patient with Niemann–Pick disease type C (NP-C) who remains free of any neurological or psychiatric manifestations 18 years after presentation — is presented. An incidental finding of massive splenomegaly was detected during a routine pelvic ultrasound. The pathology report after splenectomy showed the presence of lipid-laden macrophages. Fibroblasts cultured in LDL-enriched medium revealed abnormal filipin staining consistent with cholesterol-filled vesicles and the rate of cholesterol esterification in response to stimulation of LDL-cholesterol uptake was significantly depressed at 6% of that seen in cells from normal controls, but at a level similar to that observed in an NP-C positive control. Molecular genetic testing later revealed a compound heterozygous mutant NP-C genotype comprising two previously described disease-causing mutations in the NPC1 gene, one in exon 8 (c.1133T>C [V378A]) and one in exon 13 (c.1990G>A [V664M]). These findings confirmed the diagnosis of NP-C. Only three patients with this disorder aged >53 years have previously been reported, all of whom presented with neurological or neuropsychiatric manifestations. Our patient is the first reported NP-C patient, now in her seventh decade of life, who has to date only manifested splenomegaly. This case highlights the extreme clinical variability of NP-C, and the need to consider this disease in the differential diagnosis of organomegaly, even in the absence of neurological, psychiatric and related clinical signs. Synopsis: An elderly female patient with confirmed NP-C and isolated splenomegaly has remained asymptomatic for neurological, cognitive, psychiatric or ophthalmologic abnormailities into her seventh decade of life.