NPC can present like many different diseases, so accurate diagnosis and early intervention are critical.1,2
Early recognition of Niemann-Pick disease type C (NPC) is essential:
NPC is an ultra-rare, relentlessly progressive, and inherited disease. Its variable symptom presentation makes it difficult to diagnose.1-3
Niemann-Pick disease type C is a lysosomal storage disease (LSD) caused by mutations in either the NPC1 or NPC2 genes that occurs in approximately 1 in 100,000 live births. NPC is a progressive disease that is irreversible and ultimately fatal.3
Early recognition and diagnosis can be pivotal, as this may allow more time to access appropriate treatment.1,2
Clinical presentation of NPC is heterogeneous, with variable symptom presentations. Some features are more often seen in younger patients, while others occur mainly in adolescents and adults.2,4
Symptoms are2:
Neurological
Visceral
Psychiatric
As a rare and variable condition, NPC can be difficult to identify and accurately diagnose.4 Progression can be rapid with dramatic effects on everyday life or can develop slowly, making it difficult to notice. There is added complexity in diagnosis because NPC shares many symptoms with other more common diseases, such as1,2,5,6:
• Dyspraxia
• Cerebral palsy
• Cerebral palsy
• Parkinson’s disease
• Psychiatric disorders
• Psychiatric disorders
Niemann-Pick disease type C mechanism of disease
NPC is a lysosomal storage disease (LSD) inherited in an autosomal recessive manner that results in dysfunction of lysosomal proteins that are required for proper lipid metabolism and transport.1,3
Mutations in the NPC1 or NPC2 genes result in dysfunctional or nonfunctional NPC proteins.3
Nonfunctional and dysfunctional NPC proteins result in impaired trafficking and accumulation of lipids including unesterified cholesterol and various sphingolipids in the late endosome and lysosomes.3,4
This accumulation leads to impaired lysosomal function and dysfunction in the brain, liver, and spleen.2,3
Recognizing symptom patterns is pivotal to timely diagnosis1
The key to timely and accurate diagnosis of Niemann-Pick disease type C is identifying patterns of symptoms. Symptom presentation varies as patients age and generally affects movement, posture, mood, and memory.1
Childhood NPC frequently impacts visceral organs1,2 |
|
| Neonatal (<2 months) |
Most commonly presents as cholestatic jaundice and hepatosplenomegaly |
| Early infantile (2 months to <2 years) |
Commonly characterized by developmental milestone delay and hepatosplenomegaly |
| Late infantile (2 to <6 years) |
Commonly characterized by disturbed gait or clumsiness, and vertical supranuclear saccade palsy |
| Juvenile (6 to 15 years) |
Most commonly presents as cognitive impairment, coordination problems, seizures, and vertical supranuclear saccade palsy |
NPC progression in adults is mostly neurological1 |
|
| Adolescent/adult (>15 years) |
Commonly presents with cognitive impairment and psychiatric illness, and vertical supranuclear saccade palsy |
Symptom combinations illustrating the heterogeneity of NPC presentation might include1:
A history of jaundice at birth and slow or slurred speech
Learning difficulties and a seizure
Unsteady walking and abnormal posture
Identifying NPC as soon as possible may allow more management options and can help preserve quality of life for longer. Early diagnosis could be vital to implementation of proper comprehensive management.1
Screening tools that may lead to faster diagnosis include1:
Taking a complete medical history
Performing a clinical examination
Testing for NPC-specific blood and genetic markers
