Niemann-Pick Type C Disease: A Challenge in Diagnostics, Therapy, and Care for Affected Families

Background: Niemann-Pick disease type C (NPC) is an autosomal-recessive neurodegenerative disease characterized by the accumulation of cholesterol and glycosphingolipids.

Case Report: A 16-year-old adolescent presented with epileptic seizures, extrapyramidal movement abnormalities, and dysarthria. Unspecific features had been present for several years and included decreasing sport performance, gait disturbances, and cognitive impairment. The cMRI was normal, an ophthalmological examination was noncontributory. Lysosomal enzyme activities were normal. Chitotriosidase activity was normal in dry blood spots but slightly increased in plasma. The association of vertical supranuclear gaze palsy, mild hepatosplenomegaly, and dystonia led to the suspicion of NPC. Oxysterol concentrations in plasma were elevated; the diagnosis was confirmed by the detection of a pathognomonic compound heterozygous mutation in the NPC1 gene. In alignment with the patient and his family, we initiated substrate reduction therapy with miglustat (100 mg TID). The medication is well tolerated, and the course of disease is currently (4 months after initiation) stable.

Conclusion: Our case illustrates the challenges in clinical suspicion of NPC. Chitotriosidase activity testing in dry blood spots can be false negative. Likewise, rare and difficult to detect clinical signs such as vertical supranuclear gaze palsy can easily be overlooked. The diagnosis was confirmed by detection of a genetic mutation and targeted therapy could be initiated. Since a definite cure of NPC does not exist and the long-term therapeutic outcome is uncertain, difficulties arise in the diagnostic counseling of possibly affected family members at risk. This issue should be addressed individually with caution.