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.¹ Accumulation of these substances is toxic and causes damage to the body’s tissues, including in the brain.^1,2

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.² 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.³

NPC is a genetic condition, caused by genetic changes (variants) in either the NPC1 or NPC2 gene, with most of them being due to genetic variants in NPC1.^2,3 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.²

There are no known synonyms.

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:646 Niemann-Pick disease type C

ICD11: 5C56.0Y Other specified sphingolipidosis

The disease presentation of NPC is highly variable between individuals and can change over an individual’s lifetime.²

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.^1,4

Neurological symptoms often emerge in childhood, but in some cases, do not present until adulthood.^3,4 Symptoms 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.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

NPC is a genetic condition caused by disease-causing genetic changes (variants) in the NPC1 or NPC2 gene.^1,3,4 Majority (~95%) of individuals with NPC have genetic variants in the NPC1 gene.^1,3,4

All individuals have two copies (alleles) of their NPC1 and NPC2 genes – one on each chromosome that is inherited from each parent. NPC is an autosomal recessive condition, which means that both copies of the NPC gene must have the disease-causing genetic variants.^1,4

Individuals with the genetic variant in only one copy are unaffected but will be a carrier and may pass on that variant to their children. If both parents are carriers (each have a copy of the disease-causing variant), there is a 25% chance the child will inherit both disease-causing variants and have NPC.  More information on autosomal recessive inheritance pattern can be found at Centre for Genetics Education: Autosomal recessive inheritance.

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 about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of NPC may be made based on:

• 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 genetic variants in the NPC1 or NPC2 gene).^2,3

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.^2,3

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

Please speak to your medical team to learn more about the available diagnostic pathways for NPC.

There is currently no curative treatment for NPC. Treatment is targeted at managing symptoms (symptomatic management) which may involve a multidisciplinary care 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.³

In Australia, a substrate reduction therapy is available for treatment of the progressive neurological manifestations in adult and paediatric patients with NPC.² This drug may not be suitable for all individuals and should only be considered upon advice from your medical team.

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

Healthcare professionals involved in the treatment of NPC may include general practitioners (GP), paediatricians, geneticists, neurologists, ophthalmologists, pulmonologists, psychiatrists, physical therapists, occupational therapists, and speech therapists.^{2, 5-6} The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

We are not aware of any clinical care guidelines for NPC in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date:

• 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.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

It may be important to consider the following when managing individuals living with RD at emergency departments/services:

• 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 Childhood Dementia Disorders (Umbrella Group) – Emergency Management.

Australian NPC Disease Foundation Inc: Niemann-Pick Disease Research has information about research on NPC in Australia.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

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

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance and activities.

Australian Organisation:

Australian NPC Disease Foundation Inc (ANPDF)
Website: https://www.npcd.org.au/

The Australian NPC Disease Foundation Inc. aims to give hope, support and connection to those affected by Niemann-Pick disease type C (NPC) and Acid Sphingomyelinase Deficiency (ASMD) in Australia.

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

NPC vary between individuals, and each person’s experience is unique.

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

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

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.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on NPC, or childhood dementia disorders, can be found at:

• Australian NPC Disease Foundation Inc. (ANPDF): Newly Diagnosed
• Genetic and Rare Diseases (GARD) Information Center – Niemann Pick Disease Type C1
• Genetic and Rare Diseases (GARD) Information Center – Niemann Pick Disease Type C2
• National Organization for Rare Diseases (NORD): Niemann Pick Disease Type C
• Childhood Dementia Initiative: Knowledgebase
• RARE Portal: Childhood Dementia Disorders

• 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)
• Human Phenotype Ontology (HPO): Niemann-pick disease, type C1 (OMIM:257220)
• Human Phenotype Ontology (HPO): Niemann-pick disease, type C2 (OMIM:607625)
• 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.

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with Australian NPC Disease Foundation Inc.

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.