Niemann-Pick Type C

NP-C is a rare autosomal recessive neuro-metabolic disease that leads to a defect in cellular lipid trafficking. The intracellular accumulation of cholesterol and gangliosides particularly affects the central nervous system. The time of disease onset and initial symptoms are highly variable and can affect infants, children and adults. Early diagnosis is crucial to allow timely initiation of therapy.

Signs and Symptoms

Variable systemic, neurological and psychiatric symptoms can be observed in NP-C patients. The progressive nature of the disease leads to progressive disabling neurological problems and premature death in most patients. Vertical supranuclear gaze palsy (VSGP) with slowing of first downward and then upward saccades (saccade palsy) is one of the most specific neurological signs of NP-C, making the examination of eye movements a valuable tool for early detection of NP-C. Enlarged spleen, often accompanied by an enlarged liver, can be consistently seen in NP-C patients. In children, dystonia, gelastic cataplexy and epilepsy are frequent symptoms. Juvenile and adult patients present with cerebellar ataxia, dystonia or in late stages spasticity, along with psychiatric disorders, such as therapy-resistant psychosis or depression and develop early subcortical dementia. 

Diagnosis

NP-C often remains undetected or is misdiagnosed due to the wide range of possible symptoms. Examination of eye movement is crucial for the detection of NP-C, since VSGP is observed in more than 95% of patients. Typically, vertical downward saccades are affected first, followed by vertical upward saccades. With disease progression horizontal saccades and smooth pursuit also become impaired. Patients blink frequently and use head movement to compensate for the loss of vertical saccades. This is often one of the first signs of NP-C recognized by friends and family.

As a tool for diagnosis the NP-C Suspicion Index tool was developed by a group of NP-C experts to provide a risk prediction score and to identify patients who should undergo testing for NP-C. The tool was subsequently included in the recommendations of the NP-C Guidelines Working Group for the diagnosis and management of Niemann-Pick type C disease.

Observable ocular motor disorders

  • Vertical supranuclear gaze palsy: initially impairment of vertical (downward) saccades followed by horizontal saccades and smooth pursuit.

References

Strupp M, et al. Central ocular motor disorders, including gaze palsy and nystagmus. J Neurol 2014, 261(2):542-558. PubMed

Patterson MC, et al. Recommendations for the diagnosis and management of Niemann-Pick disease type C: an update. Mol Genet Metab. 2012;106:330–44. PubMed

Salsano E, et al. Vertical supranuclear gaze palsy in Niemann-Pick type C disease. Neurol Sci, 2012, 33:1225-1232. PubMed