Niemann-Pick Disease Type C (NPC)

Metabolic Disorders Inborn Errors of Metabolism; Lysosomal Diseases (Sphingolipidosis)

IMPORTANT INFORMATION

The information on the Rare Awareness Rare Education (RARE) Portal is intended for educational purposes only and does not replace professional advice.

Rare diseases typically display a high level of symptom complexity and variability. Individuals diagnosed with the same rare disease may be impacted differently and each person’s experience is unique. Please seek support from qualified healthcare professionals to learn more about the most suitable care and support options for you.

For more information on this disease, please refer to RVA Partner, Australian NPC Disease Foundation Inc.¹

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.

Contributors

This page has been co-developed with RVA Partner, Australian NPC Disease Foundation Inc.¹

Emergency Management

There may be special considerations for the emergency management of individuals living with NPC presenting to emergency departments.

Individuals with NPC may be at risk of aspiration pneumonia, which is life-threatening emergency.

More information relevant to emergency management of individuals with childhood dementia disorders can be found at RARE Portal: Childhood Dementia Disorders (Umbrella Group) – Emergency Management.

Clinical Care Guidelines

Consensus clinical management guidelines for Niemann-Pick disease type C, published in 2018, have been developed by the International Niemann-Pick Disease Registry (INPDR) consortium consisting of expert physicians, geneticists, allied healthcare professionals and patient support groups from 13 countries, including Australia.²

Synonyms

ORPHA:646

ICD11: 5C56.0Y Other specified sphingolipidosis

Summary

Niemann-Pick disease type C (NPC) is a type of lysosomal storage disorder (under the class of sphingolipidosis). In NPC, cells in the body are unable to properly transport cholesterol and other fatty substances (lipids), resulting in their accumulation.³ Accumulation of these substances is toxic and causes damage to the body’s tissues, including in the brain.^1,3

NPC is considered to be a childhood dementia disorder, characterised by progressive brain damage (neurodegeneration). Symptoms can be highly variable between individuals and can develop at any age of life.In some cases, NPC can be life-threatening in the first few months of life, whilst for other individuals, symptoms may not be obvious until adulthood.²

NPC is a genetic condition, caused by mutations in either the NPC1 or NPC2 gene, with majority (95%) being due to mutations in NPC1.^1,2 NPC is distinct from Niemann-Pick disease type A and B, which also results in accumulation of lipids but are instead due to a defect in breaking down (metabolism) of those lipids.¹

Please visit Australian NPC Disease Foundation Inc. (ANPDF): #NPCdiaries for video diaries of NPC families sharing their stories.

Useful Links for Professionals

GeneReviews®: Niemann-Pick Disease Type C

Orphanet: Niemann-Pick disease type C

Online Mendelian Inheritance in Man (OMIM): #257220 Niemann-Pick Disease, Type C1; NPC1

Online Mendelian Inheritance in Man (OMIM): #607625 Niemann-Pick Disease, Type C2; NPC2

Human Phenotype Ontology (HPO): Niemann-Pick disease type C (ORPHA:646)

Inborn Errors of Metabolism Knowledgebase (IEMbase): Niemann-Pick disease type C1

Inborn Errors of Metabolism Knowledgebase (IEMbase): Niemann-Pick disease type C2

Childhood Dementia Knowledgebase – a relational database that provides key statistics for each of the 100+ conditions that cause childhood dementia, including NPC.

Symptoms

The disease presentation of Niemann-Pick disease type C (NPC) is highly variable between individuals and can change over an individual’s lifetime.¹

Babies may present with jaundice, poor muscle tone (hypotonia), enlarged liver and spleen (hepatosplenomegaly), as well as liver and lung disease that can lead to life-threatening complications.^3,4

Neurological symptoms often emerge in childhood, but in some cases, do not present until adulthood.^3,4Symptoms are often progressive and may include^1-4:

Difficulty in controlling and posturing of limbs (dystonia)
Loss of muscle control leading to lack of balance, coordination and trouble walking (ataxia) – this may present as unsteadiness of gait and clumsiness
Weakness of speech muscles, resulting in slurred or slow and unclear speech (dysarthria)
Difficulty in swallowing (dysphagia); assisted feeding may be required in some cases
Difficulty with upward and downward eye movements (Vertical Supranuclear Gaze Palsy, VSGP)
Generalised loss of muscle tone whilst still conscious, triggered by laughing (gelastic cataplexy)
Seizures
Learning difficulties (cognitive dysfunction) and progressive intellectual decline (dementia)
Psychiatric disturbances, particularly in adults

Individuals with NPC may also be at risk of aspiration pneumonia, which can be life-threatening. It is an infection of the lungs caused by inhaling saliva, food, or liquid into the airway, which can be due to the inability to swallow.

Please speak to your medical team to learn more about the symptoms of NPC.

Cause/Inheritance

Niemann-Pick disease type C (NPC) is a genetic condition.^2-4 It is caused by mutations in NPC1 or NPC2 gene. Majority (~95%) of individuals with NPC have a mutation in the NPC1 gene.^2-4

Mutations in the NPC1 or NPC2 genes are inherited in an autosomal recessive manner.^3,4 Information about autosomal recessive inheritance can be found at: Factsheet: Autosomal recessive inheritance (NSW Government Health: Centre for Genetics Education)

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information on genetic counselling can be found on the National Services page and specific State and Territory Services pages on the RARE Portal.

Diagnosis

Diagnosis of Niemann-Pick disease type C (NPC) is made through:

biomarker profiling to look for increased levels of oxidised cholesterol products (oxysterols) and lyso-sphingolipids in the blood plasma, as well as bile acids in the blood plasma and urine, and
genetic testing (for mutations in the NPC1 or NPC2 gene).^1,2

Filipin staining test (which involves a skin biopsy to detect for accumulation of cholesterol) can also be used as a diagnostic tool but is no longer the first-line test for NPC.^1,2

GeneReviews®: Niemann-Pick Disease Type C (Differential Diagnosis) has information about the differential diagnoses that can be performed to rule out other conditions.

Treatment

Treatment of Niemann-Pick disease type C (NPC) mainly involves strategies to manage the symptoms, which may involve a multidisciplinary medical team. This will depend on the individual’s specific symptoms. Management strategies may consist of physical, occupational and speech therapy, as well as monitoring of growth, hearing, feeding and swallowing, bowel and bladder function, and mental wellbeing.²

In Australia, a substrate reduction therapy is available for treatment of the progressive neurological manifestations in adult and paediatric patients with NPC.¹ This drug may not be suitable for all individuals and should only be considered upon advice from your medical team.

Please speak with your medical team to learn more about suitable treatment and management strategies for NPC.

Clinical Care

Healthcare professionals involved in the treatment of Niemann-Pick disease type C (NPC) may include general practitioners (GP), paediatricians, geneticists, neurologists, ophthalmologists, pulmonologists, psychiatrists, physical therapists, occupational therapists, and speech therapists.^1,5-6 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

Research

Information about research on Niemann-Pick disease type C (NPC) in Australia can be found at Australian NPC Disease Foundation Inc.: Australian Research Updates.

Please visit Australian Clinical Trials to learn about clinical trials for NPC in Australia; there may not be any clinical trials currently available.

Information regarding clinical trials for NPC in other countries can be found at ClinicalTrials.gov; there may not be any clinical trials currently available.

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Rare Disease Organisation(s)

Australian NPC Disease Foundation Inc (ANPDF) RVA Partner Australian Organisation
Website: https://www.npcd.org.au/
Phone: +61 420 985 510
Email: [email protected]
Contact form: https://www.npcd.org.au/contact

The Australian NPC Disease Foundation Inc. is a registered charity dedicated to supporting families, raising awareness and funding research for a cure of Niemann-Pick disease type C.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

Mental Health

For information on available general mental health services, please visit the ‘Mental Health’ sections listed on the National and State Services pages.

Other

Further information on Niemann-Pick disease type C (NPC), or childhood dementia disorders, can be found at:

References

Australian NPC Disease Foundation Inc. Accessed 5 September 2023. https://www.npcd.org.au/
Geberhiwot T, Moro A, Dardis A, Ramaswami U, Sirrs S, Marfa MP et al. Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet Journal of Rare Diseases. 2018; 13(50). https://doi.org/10.1186/s13023-018-0785-7
Orphanet. Niemann-Pick disease type C. Accessed 5 September 2023. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=646
Patterson M. GeneReviews [Internet]. University of Washington, Seattle (WA). Niemann-Pick Disease Type C. 2000 [updated 10 Dec 2020]. https://www.ncbi.nlm.nih.gov/books/NBK1296/
Genetic and Rare Diseases (GARD) Information Center. Niemann-Pick disease type C Accessed 5 September 2023. https://rarediseases.info.nih.gov/diseases/7207/niemann-pick-disease-type-c1
Genetic and Rare Diseases (GARD) Information Center. Niemann-Pick disease type C2 Accessed 5 September 2023. https://rarediseases.info.nih.gov/diseases/3992/niemann-pick-disease-type-c2

Page Last Updated

13/11/2023 15:55

Metabolic Disorders Inborn Errors of Metabolism; Lysosomal Diseases (Sphingolipidosis)