Clinical symptoms of Niemann-Pick type C disease

Although Niemann-Pick type C disease (NP-C) classically presents in mid-to-late childhood, it also occurs in infants and adults.¹ The most common symptoms are shown in Figure 1.²

The symptoms of NP-C are highly variable and can be categorized according to the age of disease onset.¹

Neonatal/infantile manifestations

NP-C often goes undiagnosed in the very young as the clinical presentation is non-specific, and many infants die during the first few months of life. Symptoms include:

	Ascites in utero (via ultrasonography) that persist after birth1
	Severe liver disease with jaundice (usually with hepatosplenomegaly).1,3 The absence of organomegaly should not rule out NP-C.3
	Infiltration of the lungs with foam cells leading to pulmonary failure which is often fatal3
	Hypotonia and delayed development of psychomotor function3

Some infants show minimal, or no, hepatic or pulmonary manifestations and primarily present with hypotonia and delayed development.³ Infants can experience a complete resolution of symptoms only to present with neurological problems years later.³

Childhood manifestations

NP-C typically presents in mid-to-late childhood. ‘Classic' symptoms include: ^1,3

	Clumsiness and gait disturbance progressing to obvious ataxia
	Vertical supranuclear gaze palsy (VSGP) is a common early, and disease defining, neurological symptom
	Gelastic cataplexy in up to 50% of children
	Partial/generalized seizures in 33-54% of children
	Dystonia, eventually involving all limbs and axial muscles
	Progressive dysphagia and dysarthria - speech and swallowing are progressively affected, and oral feeding eventually becomes impossible
	Progressive and insidious cognitive decline, and behavioral problems

Adolescent and adult manifestations

Initial signs and symptoms vary but can include: ^1,4,5

	Psychiatric problems (e.g. psychosis, depression, schizophrenia-like illness), cognitive dysfunction, and/or seizures
	Ataxia, dysarthria, and dysphagia
	VSGP
	Hepatomegaly and splenomegaly in some patients

References

1. Wraith JE, Imrie J. Understanding Niemann-Pick disease type C and its potential treatment. UK Blackwell Publishing, 2007.
2. Garver WS et al. The National Niemann-Pick C1 database: report of clinical features and health problems. Amer J Med Genet Part A 2007; 143: 1204-11.
3. Patterson MC. Niemann-Pick disease Type C. Gene Reviews 2007a (updated 9 July). Accessible at: www.geneclinics.org. Accessed October 2008.
4. Imrie J, Vijayaraghaven S, Whitehouse C et al. Niemann-Pick disease type C in adults. J Inherit Metab Dis 2002; 25: 491-500.
5. Sévin M, Lesca G, Baumann N et al. The adult form of Niemann-Pick disease type C. Brain 2006; 130: 120-33.