This eBook has been developed by Actelion Pharmaceuticals Ltd as a resource to improve understanding of NP‑C. It provides a useful summary of current information about the disease, the diagnosis procedure and available treatments. It highlights the impact a diagnosis of NP‑C can have on the patient and those around them. It also outlines the strategies patients and their families can use to manage their condition as effectively as possible.
There are three other types of Niemann-Pick disease, but this resource focuses on Type C only.
The book is intended for the use of a general audience.
Understanding NP‑C
Niemann-Pick type C disease (NP‑C) is a rare, life-limiting disease caused by a build-up of lipids (fatty molecules) in the organs of the body. It can develop at any age and can cause a variety of different visceral (relating to the body’s organs), neurological or psychiatric symptoms. The progression of the disease varies greatly from person to person.
NP‑C can have a devastating impact on quality of life, and most people with NP‑C will eventually need full-time care.
Early diagnosis is vital, as treatment is available to slow the rate of progression and to alleviate the symptoms of NP‑C. Unfortunately, NP‑C is often undetected or misdiagnosed, and as a result, patients do not receive the prompt treatment and support they need.
“There were things we didn’t even notice as parents; for example, he could no longer hold the fork properly or hold his own cup, and while others would take note of that, we thought that perhaps he was simply mimicking his baby brother to attract attention”
Parent
NP‑C is an inherited disease that is caused by a build-up of lipids in the liver, brain and spleen. It can present at any age and is a progressive disease, which means that symptoms become worse over time. The age of onset (when the symptoms first appear) and rate of progression vary greatly from person to person.
NP‑C is often undetected or misdiagnosed, as there is low awareness of the disease among healthcare professionals and the symptoms of the disease are non-specific.
A diagnosis of NP‑C can have a profound impact on the lives of patients and their families, whatever their age.
Advances in the understanding of NP‑C have led to the development of a NP‑C-specific treatment that can slow the disease progression. The aim is to help patients continue their everyday functions and maintain quality of life for as long as possible.
What is NP‑C?
Where does the name Niemann-Pick come from? What is the role of lipids in NP‑C?
Niemann-Pick was named after the two doctors who first identified the disease in the early 1900s.
There are four types of Niemann-Pick disease: A, B, C and E. Originally, there was also a type D but this has now been re-classified as a variant of type C. This eBook focuses on Niemann-Pick type C (NP‑C) only.
All types of Niemann-Pick disease are caused by changes to the way lipids are stored in the body, but the organs affected and symptoms vary from type to type.
Lipids are fatty molecules such as cholesterol and glycosphingolipids.
They are vital to many organs in the body.
Normally, the body is able to process lipids efficiently, and this keeps levels within normal limits.
In patients with NP‑C, the movement and storage of lipids becomes disrupted. The fatty molecules become trapped and start to build up in different organs of the body.
In people with NP‑C, excess lipids build up in different parts of the body, including the brain, liver and spleen.
This can lead to cell damage, which can result in a variety of symptoms, ranging from visceral symptoms such as prolonged jaundice and enlargement of the liver, to neurological symptoms like eye movement disorders, balance and muscle disorders, difficulty swallowing and seizures or psychiatric symptoms such as early-onset psychosis, paranoid delusions, and hallucinations.
The symptoms experienced will depend on the area affected by the build-up of lipids.
What causes NP‑C?
NP‑C is caused by an inherited change (mutation) in one of two genes: NPC1 or NPC2. These genes produce a protein that plays an important role in the processing of fatty molecules within the cells of certain organs.
In NP‑C, the protein is damaged, which causes the fatty molecules to become trapped within the cell. NP‑C is described as a lysosomal storage disorder, as the NP‑C protein is located in the cell membrane of a small compartment called a lysosome.
When fatty molecules accumulate in the brain, they damage the nerve cells (neurons), causing them to change shape, grow abnormally or die. This can lead to the neurological symptoms of NP‑C, such as seizures or problems with eye movement, balance or speech.
Lipids can also build up in the liver and/or spleen, causing abnormal enlargement of these organs (the spleen is an organ deep in the abdomen). This is seen most often in children with NP‑C and presents as a swollen abdomen. It is more difficult to recognize the swollen abdomen in adults, and if NP‑C is suspected an ultrasound scan is usually performed to confirm the swollen abdomen.
How is NP‑C inherited?
How is genetic information passed on? What is the probability of having a child with NP‑C and what is the role of genetic testing?
We all have 22 pairs of autosomes (chromosomes that are not involved in the determination of gender). These carry genetic information such as hair and eye color and other characteristics from one generation to the next.
Chromosomes contain numerous genes, which carry the information that determines our genetically determined characteristics, the so-called traits.
Genes come in pairs – with one gene in the pair coming from the mother, the other from the father.
Some diseases are caused by just one damaged or altered gene in the pair, passed on from just one parent. In NP‑C, both genes in the pair must be abnormal for the disease to develop.
People with only one abnormal gene in the pair are called carriers. For a child with NP‑C, both parents will be carriers of the disease, but as they each have one normal gene in the pair, they themselves will not have symptoms of NP‑C.
A genetic test can help identify if there is a change (mutation) in a particular gene or chromosome.
It can be difficult to decide whether to have a genetic test. Genetic counselling can help people cope with some of the emotions and implications of being tested. Healthcare professionals can provide further information on this subject.
People with a relative who has an inherited condition may be tested to see if they have the condition or are a carrier.
Genetic testing is usually offered to patients with NP‑C and to family members.
It is also used to confirm a diagnosis of NP‑C.
It can take several months to identify the NP‑C gene faults initially, but testing of other family members is usually much quicker.
Genetic testing takes the form of a blood or tissue sample.
Signs and symptoms of NP‑C?
The symptoms of NP‑C vary widely and depend on which organs the fatty deposits are located in.
Symptoms can develop at different ages and in different combinations, which explains why NP‑C is often undetected or misdiagnosed.
Broadly speaking, symptoms fall in three categories: visceral, neurological, and psychiatric. Healthcare professionals may not immediately pick up on these symptoms when they are described to them in everyday language (e.g. “is clumsy” or “speaks slowly”), which can delay diagnosis.
Visceral means relating to the body’s organs. These symptoms are seen most often in very young children with NP‑C and present as a swollen abdomen. They can also occur in adults, but are more difficult to recognize. Visceral symptoms include:
Enlargement of the liver (hepatomegaly)
Jaundice in newborns, which is very common and therefore often not immediately associated with NP‑C
Enlargement of the spleen (an organ deep in the abdomen) (splenomegaly)
The neurological symptoms of NP‑C do not usually develop before the age of 3 months, and some may not become apparent until adulthood. Many of these symptoms are not specific to NP‑C, which can delay diagnosis.
On average, NP‑C is diagnosed five to six years after the initial appearance of neurological symptoms, which can be extremely frustrating for patients and their families. These symptoms include:
Episodes of sudden muscular weakness during moments of strong emotion (gelastic cataplexy)
Inability to rapidly move eyes up and down voluntarily (vertical supranuclear gaze palsy). This symptom is present in almost all NP‑C patients, but is often undetected although it is easy to test for.
Involuntary muscle contractions causing abnormal twisting or posture (dystonia)
Slurred and irregular speech (dysarthria)
Difficulty swallowing (dysphagia)
Balance disorder, clumsiness and frequent falls (ataxia)
Decreased muscle tone (hypotonia)
Seizures
Delayed developmental milestones in young children
Hearing loss
Learning difficulties
Problems with information processing or memory (cognitive dysfunction)
Gradual change in normal brain function and abilities including memory, thinking, language, judgment and behavior (dementia)
Physicians who suspect that a patient may have NP‑C can use the NP‑C Suspicion Index, a tool to help them to assess the likelihood of the disease. This index ranks the different categories of signs and symptoms of NP‑C and takes into account family history to provide a risk prediction score for each patient. Patients who scored highly should be referred to a specialist centre for diagnostic testing.
NP‑C is a rare disorder. It is estimated to affect 1 in every 90,000 newborn children, although this may be a low estimate.
What is the outlook for people with NP‑C?
NP‑C is a progressive disease, which means that symptoms become worse over time and most patients will eventually require full-time care. Advances in the understanding of NP‑C have led to the development of a NP‑C-specific treatment that can slow the disease progression, so early diagnosis is vital to get patients the support they need.
Diagnosis and treatment of NP‑C
NP‑C is a rare disease and many healthcare professionals are unfamiliar with it.
The symptoms of NP‑C vary from person to person and present at different stages and in different combinations. They may appear to be unconnected, and often no link is made between different symptoms. This can unfortunately lead to significant delays in diagnosis: NP‑C is frequently under-diagnosed and under-treated.
For many patients, diagnosis is a long, frustrating process. The average delay in diagnosis is 5-6 years from the onset of neurological symptoms. Often, the delay is much longer and in some cases, the correct diagnosis is only made thanks to the sheer persistence of parents and families in pushing for further tests.
When NP‑C is suspected, the availability of new, more sensitive diagnostic tests is speeding up the diagnosis process.
“… IT FELT AS IF NO ONE WAS TAKING ME SERIOUSLY. I REALLY HAD TO BANG MY FIST ON THE TABLE TO GET SOME RECOGNITION.”
PARENT
“Under the circumstances, it was a relief to find out fast that our daughter has Niemann-Pick type C disease. It meant that she was able to get the right treatment quickly, and it’s given us a clear pathway of how her disease should be managed. As a parent, there is nothing worse than seeing your child suffer, and there is nothing you can do because you don’t know what is wrong with them.”
Parent
What tests are used to diagnose NP‑C?
Biomarker blood tests (e.g. oxysterol and lysosphingomyelin-509): Increasingly, NP‑C-specific blood tests are being used to diagnose the disease. These are sensitive and specific to NP‑C and are helping to provide more accurate, faster results. Diagnosis can be confirmed via genetic testing, where a DNA test is carried out to detect the abnormal genes associated with NP‑C.
To assess the symptoms of NP‑C, patients may have one or more of the following tests:
A small sample of skin is removed, usually under local anesthetic. The tissues cells are cultivated for several weeks to determine whether there is a build-up of NP‑C specific fatty molecules.
A scan used to measure brain activity. During this test electrodes are attached to the scalp. It may be used to understand why a patient is having seizures or suffering from confusion.
A scan that used magnetic and radio waves to look inside the body. In NP‑C, MRI scans are used to detect changes in the brain.
The challenge of making the right diagnosis
Many of the symptoms of NP‑C are non-specific and may be attributed to other diseases.
Patients may be seeing more than one specialist to investigate apparently unconnected symptoms, and it may take time to make the link between symptoms.
These factors can lead to delays in diagnosis of NP‑C. The average time today is 5-6 years after the start of neurological symptoms.
Some symptoms, such as learning difficulties, develop gradually and may not be recognized as a symptom of NP‑C for many years.
Psychiatric symptoms, such as hallucinations or delusions, often emerge during teenage years, before any physical symptoms are apparent. They are often initially misdiagnosed as schizophrenia, autism or bipolar disorder.
In some cases, a great deal of persistence is needed to get to the correct diagnosis. The patients’ families play an important role in this process by sharing observations about present and past symptoms, information on the medical family history etc.
What treatments are used to diagnose NP‑C?
NP‑C is a progressive disease, which means that symptoms become worse over time and most people will eventually require full-time care. Advances in the understanding of NP‑C have led to the development of a NP‑C-specific treatment that can slow disease progression, so early diagnosis is vital to get patients the support they need.
There are three broad categories of treatments: medication specifically for NP‑C, medicines used to relieve symptoms, and occupational therapy.
NP‑C is progressive, so it is important to start treatments as soon as possible to allow patients to maintain the best possible quality of life.
Research in the field of NP‑C is ongoing, and this may lead to the introduction of new treatments in the future.
Zavesca (miglustat) is an enzyme inhibitor that works by reducing the build-up of lipids in patients with NP‑C. In the European Union, Zavesca is indicated for the treatment of progressive neurological manifestations in adult patients and pediatric patients with Niemann-Pick type C (NP‑C) disease. Zavesca is commercially available for the treatment of Niemann-Pick type C disease in 46 countries, including the European Union since 2009 and Japan since 2012.
This consists of structured activities designed to allow patients to reach their maximum level of independence and function.
It is used to improve mobility, posture and speech.
The impact of NP‑C
“THE DIAGNOSIS IS LIKE YOUR HOUSE OF CARDS COLLAPSES. ESPECIALLY ONCE YOU TYPE ‘NIEMANN-PICK C’ INTO THE SEARCH ENGINE. YOU FIND OUT WHAT IT IS AND YOU THINK: ‘MY GOD, WHY DID THIS HAVE TO HAPPEN TO US?’”
PARENT
NP‑C can have a devastating impact on the life of patients and their family and friends. Symptoms and the rate of progression vary, so each patient will have a different way ahead of them.
NP‑C can severely affect many aspects of daily life, from studying and employment to basic functions such as speech and swallowing. The right level of support, treatment and care can help patients to have the best possible quality of life.
NP‑C often affects young children and teenagers, and thus can have a severe impact on schooling and study, with full-time classroom support required as the disease progresses.
Cognitive symptoms associated with NP‑C, such as problems with processing information and changes to behavior, can cause a decline in school performance and can lead to children being labeled ‘difficult’ or ‘disruptive’ before they are correctly diagnosed. This can be distressing for both children and parents.
It is unlikely that those diagnosed with NP‑C in their late teens or early adulthood will be able to maintain full-time employment. Depending on the severity of the disease, they may require full-time care.
Social workers and patient associations should be able to advise on financial benefits available to families affected by NP‑C in their country.
“Receiving a diagnosis of NP‑C can be extremely emotional, and it is important for families to understand that they are not alone in this.”
Niemann-Pick Disease Nurse Specialist
Coming to terms with a diagnosis of NP‑C is very difficult for the person living with the disease and their family and friends. They will usually face a steep learning curve as most will never have even heard of NP‑C.
Emotions are likely to change over time as the person living with NP‑C and their family learn to accept the situation or as new issues arise. Many families have described the process as a rollercoaster.
For some parents, there may actually be a sense of relief to finally have a diagnosis after years of tests without answers, or if their children have been labeled as ‘difficult’. The diagnosis helps to remove uncertainty and makes it possible to plan ahead.
Patients and their families will need to adjust their expectations and set new goals and objectives.
Parents may feel responsible in some way for passing the disease onto their child or may regret having disciplined a child for what they regarded as bad behavior. Or they may feel guilty that they did not notice symptoms earlier.
Diagnosis can put a strain on family life and change the family dynamic. As the patient becomes more dependent, other family members will have to take on the role of caregiver.
Hollie and Annie's story
For more stories of families and their experiences of living with NP-C, please visit:
“…REMAIN AS CALM AS POSSIBLE GIVEN THE SITUATION AND NOT TO GET OVERWHELMED ANY MORE THAN IS NECESSARY … TAKE EACH DAY AS IT COMES, BECAUSE NOT ALL THE PROBLEMS HAPPEN AT ONCE AND YOU CAN RESOLVE THEM ONE BY ONE AS THEY HAPPEN. YOU CAN’T DO ANY MORE THAN THIS”
PARENT
People affected with NP‑C may find these strategies helpful in coming to terms with the situation and better managing the disease.
Living with NP‑C is challenging and overwhelming at times, for both patient and caretaker. Most of those affected will need support from family and friends. It is usually best to be honest about those feelings. This makes it easier for others to give appropriate support.
Deciding when to tell extended family about an NP‑C diagnosis is a personal decision - some people might prefer to have more information than others. Healthcare professionals may be able to advise on the best ways of sharing information.
Some people may find it helpful to arm themselves with as much information as possible about the disease, but the sheer volume of information about treatments and appointments can be overwhelming at times.
It can be helpful to keep as organized as possible, with all information kept together in one place, and to keep a notebook to jot down any questions or points to discuss with healthcare professionals at the next appointment.
The level of support for families affected by NP‑C varies greatly from country to country. Local associations and healthcare professionals are often a good source of information about benefits, grants, social services and other resources.
Mobility aids or household items such as special cutlery can make day-to-day life much easier for some patients.
If necessary, it may be possible to arrange for adaptations to the home to make daily life easier. Grants may be available to fund this.
“I try to reassure families that although they may fear the worse when hearing the diagnosis, talking to someone who understands the condition can really help.”
Niemann-Pick Disease Nurse Specialist
A diagnosis of NP‑C can be life-changing, and it may be difficult to look to the future with any confidence. It is usually best to focus on the present and to take one day at a time.
It is natural to feel shock and grief, but it is usually possible to find ways of coming to terms with the ‘new reality’, although this may take time.
A diagnosis of NP‑C will inevitably change some aspects of everyday life, but it does not define a person. Setting realistic goals and focusing on what it still possible can make it easier to maintain a more positive outlook.
Some topics can be difficult to discuss with family and friends. If this is the case, it is sensible to ask to be referred to a counselor.
Some people find it helpful to attend support group meetings or to join online forums. Communicating with other people in a similar situation can help to avoid feelings of isolation.
This resource has been developed by Actelion Pharmaceuticals in order to provide an environment to deliver a better understanding of Niemann-Pick Type C (NP‑C) and to pool information regarding the disease, the diagnosis procedure, available treatments and the impact it could have on the life of someone diagnosed with NP‑C. The resource is for use by a general audience.
The information in this resource is not intended as a substitute for advice/treatment by a physician, whose instructions should always be followed. Neither does the information provided constitute an alternative to advice from a doctor or a pharmacist and should not be used on its own to produce a diagnosis or to commence or cease a particular treatment.
The links provided are for informational purposes only; they do not constitute an endorsement or an approval from Actelion Pharmaceuticals Ltd of the services or opinions of the corporation, organization or individual. Actelion Pharmaceuticals Ltd bears no responsibility for the accuracy, legality or content of the external sites or subsequent links. You are requested to contact the respective external site for answers to questions regarding its content.
The information provided is valid on the publication date but may be subject to further modifications. Even though Actelion aims to provide accurate and up to date information at all times, please acknowledge that the present resource is made available “as is”. Actelion does not give any warranty or representation, whether expressly stated or implied, of any kind related to the comprehensiveness, usefulness, reliability or timelines of the content of this resource. Actelion cannot be held liable for any direct or indirect damage of a material or non-material nature that might be caused by the use or non-use of the information presented.
