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Differential diagnosis of Niemann-Pick type C disease

The differential diagnosis of Niemann-Pick type C (NP-C) is broad due to its wide-ranging clinical presentation.1 The common visceral symptoms such as neonatal jaundice, isolated splenomegaly or hepatosplenomegaly and neurologic signs seen in patients with NP-C can also arise in other diseases caused by inborn errors of metabolism. These include Sandhoff disease, Gaucher disease type 3 (GD3) and ASM-deficient Niemann-Pick disease (NP-A/B).2

Other diseases to be aware of and assess for differential diagnosis include:2

·       Wilson's disease and some other metal storage disorders;

·       Idiopathic neonatal hepatitis and other causes of cholestatic jaundice;

·       ASM deficiency;

·       Psychosis, bipolar disorder, depression, atypical schizophreniform disorders and/or other psychiatric signs including attention deficit disorder, Asperger-like presentations and a dysexecutive syndrome;

·       Huntington's disease (HD), Gerstmann–Sträussler–Scheinker syndrome or progressive supranuclear gaze palsy (PSP).

In order to achieve a fast and differential diagnosis of NP-C, it is important for healthcare professionals to link together the visceral, neurologic and psychiatric symptoms that a patient might present with.

Differential diagnosis algorithms are currently in development for patients presenting with ataxia or ocular motor signs. The algorithms closely follow clinical practice, evaluate clinical and paraclinical signs and symptoms, and ultimately provide a list of potential diagnoses. These differential diagnostic algorithms, hold great promise as easy-to-use clinical tools, to aid diagnosis of patients with challenging symptom presentations.


  • The NP-C Suspicion Index is a simple-to-use screening tool to help identify patients who should be tested for NP-C to aid earlier diagnosis.3 The new NP-C SI is available for patients aged 0–4 years (NP-C SI0–4 years) and those aged >4 years (NP-C SI>4 years).

    Actelion Pharmaceuticals Ltd has developed three masterclasses, which are available to healthcare professionals to support recognition of possible atypical signs and symptoms in their patients. For more information about these masterclasses, please visit educational resources. provides detailed information on ocular motor and vestibular disorders, associated brain structures, underlying conditions, and best practice guidance for eye movement examination. 

    The NP-C Professional Network is a global network of healthcare professionals, dedicated to the treatment of NP-C. The network provides a platform for connection of healthcare professionals internationally, exchange of knowledge, sharing of individual experiences and information regarding the latest updates from the NP-C field.




  1. Wraith E, Baumgartner M, Bembi B, et al. Recommendations on the diagnosis and management of Niemann-Pick disease type C. Mol Gen Metab 2009;98:152–65.
  2. Patterson MC, Hendriksz CJ, Walterfang M, et al., on behalf of the NP-C Guidelines Working Group. Recommendations for the diagnosis and management of Niemann–Pick disease type C: An update. Mol Genet Metab 2012;106:330–44
  3. Wijburg FA, Sedel F, Pineda M, et al. Development of a suspicion index to aid diagnosis of Niemann-Pick disease type C. Neurology 2012;78:1560–7.