Distinct Niemann-Pick Disease Type C Clinical, Cytological, and Biochemical Phenotype in an Adult Patient With 1 Mutated, Overexpressed NPC1 Allele

• Autor(a) principal: Jecel,Julia
• Data de Publicação: 2015
• Outros Autores: Harzer,Klaus, Paschke,Eduard, Beck-Wödl,Stefanie, Bauer,Peter, Hejtman,Milos, Katzenschlager,Regina
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of Inborn Errors of Metabolism and Screening
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2326-45942015000100303
• topic: Niemann-Pick disease type C; bone marrow storage cells; allele overexpression; cholesterol storage; heterozygous manifestation

Abstract Niemann-Pick disease type C (NP-C) is a rare autosomal-recessive neurovisceral lysosomal storage disease. We report on a juvenile onset, now 25-year-old female patient with typical neurologic symptoms, including vertical gaze palsy, of NP-C. The diagnosis was supported by a positive filipin test (“variant biochemical phenotype” of cholesterol accumulation) in cultured fibroblasts, high numbers of “Niemann-Pick cells” in the bone marrow, and 1 positive out of 3 NP-C biomarkers tested, but NP-C was not definitely confirmed genetically. She showed only 1 known NPC1 variant (3 bp deletion in exon 18; p.N916del); this allele, however, being distinctly overexpressed at the messenger RNA level as compared to the wild-type allele, as a not as yet clarified (copathogenic?) phenomenon. The patient’s mother, also carrying the p.N916del allele but without overexpression, has a chronic inflammatory disease of the central nervous system classified as multiple sclerosis. However, her severe clinical phenotype includes some signs also consistent with NP-C. The laboratory diagnosis of NP-C can be challenging in detecting novel disease constellations.