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.

KEYWORDS:

• Niemann–Pick disease type C (NP-C)
• adolescent
• adult
• diagnosis

Acknowledgements

We are grateful and thankful to Elisa Dalmonte (Actelion employee) for reviewing the English manuscript. The editorial assistance of Matthew Reilly PhD at InTouch Medical Ltd, paid for by Actelion Pharmaceuticals Ltd, is also appreciated.

Declaration of interest

V. Di Lazzaro, M. Marano, and L. Florio have no conflicts of interest to declare. S. De Santis is a full-time employee of Actelion Pharmaceuticals Italia Srl. The authors alone are responsible for the content and writing of the, contributed to the development of the manuscript, and are responsible for the content of the paper.

No potential conflict of interest was reported by the authors.