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Symptoms of Niemann-Pick type C disease

Niemann-Pick type C disease (NP-C) is characterized by a number of highly variable clinical symptoms that can be categorized as visceral (systemic), neurological or psychiatric. The most common symptoms are shown in Figure 1. One of the strongest indicators of NP-C is when a patient presents with symptoms in more than one of these categories.1 Therefore, linking these symptoms together can facilitate fast and differential diagnosis of NP-C.

Figure 1: Symptoms of NP-C2,3

 

Visceral symptoms Neurological symptoms Psychiatric symptoms
Hepatomegaly Vertical supranuclear gaze palsy (VSGP) Early-onset psychosis
Splenomegaly Ataxia, clumsiness or frequent falls Prominent visual hallucinations
Prolonged neonatal jaundice Dysphagia Treatment-resistant psychiatric symptoms
Pulmonary infiltrates (in NPC2 mutations or early onset NP-C) Dysarthria Pre-senile cognitive decline and/or dementia
Fetal hydrops Dystonia Disruptive or aggressive behavior in adolescence or adulthood
Fetal ascites Gelastic cataplexy Cognitive dysfunction
Neonatal cholestasis Acquired and progressive spasticity  
  Hypotonia  
  Delayed developmental milestones  
  Seizures (partial or generalized)  
  Myoclonus  
  Deafness  
 

NP-C is commonly undetected or misdiagnosed due to its heterogeneous clinical presentation characterized by a wide range of symptoms that individually are not specific to the disease.

Interviews with patients and carers as well as healthcare professionals as part of the NP-C Patient and Healthcare Professional Survey confirmed that, in general, an early diagnosis of NP-C depends on individual symptoms, which occur sequentially, being linked together and then linked to the possibility of NP-C.4

Vertical supranuclear gaze palsy (VSGP) is the most common neurological sign of NP-C but is often missed in the initial differential diagnosis (and rarely detected in early infancy). Vertical saccadic eye movement (SEM) impairment is affected first followed by horizontal SEM impairment. When examining a patient it is important to test their ability to follow an object but also to test the voluntary saccades by asking the patient to spontaneously move their gaze up and down between two objects.

The research indicates that encouraging specialist healthcare professionals to discuss symptoms with colleagues in other disciplines as well as prompting parents to share more background information about their child’s illness would facilitate earlier diagnosis and accelerate access to treatment which can stabilize the progression of NP-C and potentially improve, or maintain, quality of life.2

For more information about the symptoms of NP-C, please visit symptomatic manifestations of Niemann-Pick type C disease.

Resources

  • A series of Signs & Symptoms cards are available, which summarize the typical symptoms that might alert neurologists, pediatricians, metabolic disease specialists and psychiatrists to the possibility of NP-C and prompt further investigation and referral.
  • A new screening tool has been developed by international experts to help identify patients suspected of having NP-C, with a view to establishing better and earlier diagnosis. To find out more about this tool, please visit www.NPC-SI.com.1

 

References

  1. 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(20):1560-7.
  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(3):330-344.
  3. Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis 2010;5:16.
  4. Klünemann H, Wraith E, Wijburg F. Niemann-Pick Type C Disease – Report on Results from the Niemann-Pick Type C Patient and Healthcare Professional Survey. Eur Neurol Rev 2011;6(1):12–15.