title: Niemann-Pick type C: focus on the adolescent/adult onset form.
abstract: Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment.
authors.affiliation: a Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine , Università Campus BioMedico di Roma , Rome , Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Lazzaro
authors.affiliation: a Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine , Università Campus BioMedico di Roma , Rome , Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Marano
authors.affiliation: a Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine , Università Campus BioMedico di Roma , Rome , Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Florio
authors.affiliation: b Medical Department, Actelion Pharmaceuticals , Milano , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: De Santis
mesh_terms: D000293:Adolescent; D000328:Adult; D006801:Humans; D052556:Niemann-Pick Disease, Type C / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy
keywords: Niemann–Pick disease type C (NP-C); adolescent; adult; diagnosis