Paediatria Croatica, Vol. 58 No. 4, 2014.
Izvorni znanstveni članak
https://doi.org/10.13112/PC.2014.45
Niemann-Pick disease type C: mutations of NPC1 gene and the course of disease
Ljerka Cvitanović-Šojat
; KBC Sestre milosrdnice
Maša Malenica
Kukuruzović mONIKA
Tamara Žigman
Kristina Kužnik
Ana Bielen
Sažetak
Niemann-Pick disease type C (NP-C) is a rare autosomal recessive disorder caused by mutations in the NPC1 gene in 95% of cases.
Consequently, unesterifi ed cholesterol accumulates in late endosomes/lysosomes causing extremely varied neurovisceral symptoms.
For many countries including Croatia, there are no reported NP-C cases to date, mainly because the accurate diagnosis of NP-C
requires not easily accessible biochemical and molecular-genetic laboratory tests. Therefore, with the aim to improve clinical practice
and understanding of NP-C in the region, we present the fi rst siblings with NP-C recorded in Croatia. The diagnosis was based on
histologic, biochemical and genetic tests. Namely, fi lipin staining showed accumulation of unesterifi ed cholesterol and cultured skin
fi broblasts were defi cient in esterifi cation of exogenously administered cholesterol. Electron microscopy of skin biopsy revealed the
presence of sequestrated lipids in lysosomes. Molecular analyses showed both siblings to be compound heterozygotes for two
disease-causing mutations of NPC1 protein, N1156S and Q922X. Based on comparison with previously reported N1156S homozygotes,
we propose that Q922X mutation, causing the formation of a truncated NPC1, has a more severe impact on clinical outcome.
Further, we observed pronounced diff erences in the disease course in the siblings; i.e. in the boy we observed an earlier onset and a
much faster neurologic deterioration (late infantile onset), suggesting other genetic and/or environmental factors infl uencing the
course of the disease. In contrast, the girl exhibited juvenile type of NP-C. In conclusion, when progressive neurologic symptoms
develop in late childhood and with a previous history of neonatal cholestasis, the classic late infantile or juvenile type of NP-C must
be suspected.
Ključne riječi
Niemann-Pick Disease, type C; siblings; NPC1 protein, human
Hrčak ID:
142328
URI
Datum izdavanja:
23.12.2014.
Posjeta: 3.709 *