title: The Spectrum of Niemann-Pick Type C Disease in Greece.
abstract: Niemann-Pick type C disease (NPC) is a neurovisceral lysosomal storage disease caused by mutations in either the NPC1 or the NPC2 gene. It is a cellular lipid trafficking disorder characterized by the accumulation of unesterified cholesterol and various sphingolipids in the lysosomes and late endosomes, and it exhibits a broad clinical spectrum. Today, over 420 disease-causing mutations have been identified in the NPC1 and the NPC2 genes. We present the clinical, biochemical, and molecular findings in 14 cases diagnosed in Greece during the last 28 years. Age at diagnosis ranged from 2.5 months to 48 years. Systemic manifestations were present in 7/14 patients. All developed neurological manifestations (age of onset 5 months to 42 years). Six patients are still alive (age: 5-50 years). Classical filipin staining pattern was observed in all but four patients (3 NPC1, 1 NPC2). The rate of LDL-induced cholesteryl ester formation was severely reduced in 4/7 and significantly reduced in 3/7 patients studied. Increased chitotriosidase activity was observed in 9/12 patients. Mutation analysis in 11 unrelated patients identified 12 different mutations in the NPC1 gene: eight previously described p.E1089K (c.3265G>A), p.F284Lfs*26 (c.852delT), p.A1132P(c.3394G>C), del promoter region and exons 1-10, p.R1186H (c.3557G>A), p.P1007A (c.3019C>G), p.Q92R(c.275A>G),p.S940L (c.2819C>T), and four novel ones: (p.N701K fs*13 (c.2102-2103insA), p.K1057R (c.3170A>G), IVS23+3insT(c.3591+3insT), p.C1119*(c.3357T>C); and the previously described IVS2+5G>A(c.190+5G>A) mutation in the NPC2 gene. All patients were of Greek origin. Assuming a birth rate of 100,000/year, a rough incidence estimate for NPC disease in Greece would be 0.5/100,000 births.
authors.affiliation: Department Enzymology and Cellular Function, Institute of Child Health, Athens, 11527, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Mavridou
authors.affiliation: Department Enzymology and Cellular Function, Institute of Child Health, Athens, 11527, Greece.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Dimitriou
authors.affiliation: Laboratoire Gillet-Mérieux et Neurogénétique Moléculaire, Groupe Hospitalier Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: Marie T
authors.initials: MT
authors.lastname: Vanier
authors.affiliation: Department of Genetics, University of Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Lluisa
authors.initials: L
authors.lastname: Vilageliu
authors.affiliation: Department of Genetics, University of Barcelona, CIBERER, IBUB, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grinberg
authors.affiliation: Laboratoire Gillet-Mérieux et Neurogénétique Moléculaire, Groupe Hospitalier Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Latour
authors.affiliation: 1st Department Pediatrics University of Athens, Aghia Sofia Children's Hospital, Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Xaidara
authors.affiliation: 1st Department Pediatrics University of Athens, Aghia Sofia Children's Hospital, Athens, Greece.
authors.forename: Lilia
authors.initials: L
authors.lastname: Lycopoulou
authors.affiliation: 3rd University Department of Neurology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Sevasti
authors.initials: S
authors.lastname: Bostantjopoulou
authors.affiliation: 1st Department Pediatrics, Aristotle University, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Zafeiriou
authors.affiliation: Department Enzymology and Cellular Function, Institute of Child Health, Athens, 11527, Greece. ecfdept@ich.gr.
authors.forename: Helen
authors.initials: H
authors.lastname: Michelakakis