Adult-Onset Niemann–Pick Disease Type C: Rapid Treatment Initiation Advised but Early Diagnosis Remains Difficult

Abstract

Niemann–Pick type C disease (NP-C) presents with heterogeneous neurological and psychiatric symptoms. Adult onset is rare and possibly underdiagnosed due to frequent lack of specific and obvious key symptoms. For both early and adolescent/adult onset, the available data from studies and case reports describe a positive effect of Miglustat (symptom relief or stabilization). However, due to the low frequency of NP-C, experience with this therapy is still limited. We describe two adult-onset cases of NP-C. In both cases, vertical supranuclear gaze palsy was not recognized at symptom onset. Correct diagnosis was delayed from onset of symptoms by more than 10 years. The video demonstrates the broad spectrum of symptoms in later stages of the disease. Compared with published data, the treatment outcome observed in our cases after delayed initiation of Miglustat therapy was disappointing, with continuing disease progression in both cases. Thus, early treatment initiation could be necessary to achieve a good symptomatic effect. Hence, early biochemical testing for NP-C should be considered in patients suffering from atypical neurological/neuropsychological and psychiatric symptoms, even in cases of uncertainty.

Niemann–Pick type C disease as proof‐of‐concept for intelligent biomarker panel selection in neurometabolic disorders

“…Additionally, early detection is paramount for patients with disorders affecting the developing brain or resulting in neurodegeneration in order to achieve the best clinical outcomes. 3 This is more pertinent in the current era of personalized medicine, where an ever-increasing number of novel, targeted, and diseasespecific therapeutic approaches are becoming available for neurological diseases that in the past were considered untreatable. [4][5][6] Disease-relevant biomarkers can greatly facilitate timely diagnosis and disease monitoring.…”

Mitochondrial Targeting Involving Cholesterol-Rich Lipid Rafts in the Mechanism of Action of the Antitumor Ether Lipid and Alkylphospholipid Analog Edelfosine

“…This disease is caused by mutations of the NPC1 (accounting for 95% of NP-C cases) or the NPC2 gene (5% of NP-C cases). Currently, there is no cure for NP-C and patients usually die before adulthood (frequently in the second decade of life), but adult forms of NP-C are being increasingly recognized, having a more insidious onset and slower progression [136,137]. NP-C is characterized by impaired cholesterol efflux from late endosomes and lysosomes, and secondary accumulation of lipids due to mutations in the NPC1 or NPC2 proteins, which act in coordination to mediate the efflux of unesterified cholesterol from lysosomes or late endosomes.…”

Patient with Niemann-Pick disease type C: over 20 years' follow-up

“…Miglustat therapy [6][7][8] was started at the age of 32 years. Improvements in swallowing capacity and in muscle tonus were observed.…”