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.
|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|
|Delayed developmental milestones|
|Seizures (partial or generalized)|
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.
- 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.
- 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.
- Vanier MT. Niemann-Pick disease type C. Orphanet J Rare Dis 2010;5:16.
- 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.