Overview

Some people might have heard of Niemann Pick Disease from a novel called  ‘The Memory Book’ by Lara Avery, which provides an insight into the life of a teenage girl, Samantha, who is suddenly diagnosed with Niemann-Pick. Samantha’s story reflects that of countless children and young adults whose lives are changed by their Niemann-Pick diagnosis. For them, such a diagnosis can signify an early death. 

You or someone you know may be going through a similar situation. It can be very difficult to process, but it is important to know that it can be possible to maintain a sense of normality in your life.

What is Niemann-Pick disease?

Niemann-Pick disease (NPD) is an autosomal recessive genetic disease, meaning the condition affects your body’s ability to break down membrane lipids, or transport cholesterol in your cells.¹ These fats accumulate over time and eventually lead to cell death.

As more cells die, your body is unable to replace them. So, the condition worsens over time, consequently becoming fatal. 

Symptoms

Some symptoms that people with NPD can experience include:

• Bigger liver or spleen. The build up of fats in these cells causes them to expand before they become irreparably damaged.¹ This damage can result in mass cell death, ultimately leading to organ failure
• Loss of muscle control. This can affect all muscles in the body due to nerve damage. It can manifest as slowed or stiff movements, muscle weakness, and speech difficulties
• Lung disease or repeated lung infections
• Neurological deterioration, such as a decline in learning and/or memory (dementia), changes in behavior and mental health conditions 
• Vision and hearing loss
• Low platelet count (thrombocytopenia), which can cause excessive bleeding¹

Symptoms depend on the type of NPD you have.

Types of Niemann-Pick disease

There are 3 main types of NPD: type A, B, and C. Types D, E and F have previously been named but are no longer used.²

Types A and B

Niemann-Pick types A and B are present in 1 in 250,000 people, and it is thought that people with an Ashkenazi Jewish background have a higher risk of developing NPD A or B.¹

Type A is usually diagnosed in newborns and infants, and it is extremely severe, with a life expectancy of a couple of years after diagnosis.On the other hand, type B is usually less severe than type A. It often presents in childhood, and is characterized by symptoms in visceral organs, such as the liver and lungs. It is distinct from type A as it appears to have no effect on the central nervous system.³ This means that learning and memory are usually unaffected in people with NPD type B.

Both A and B are caused by mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene. This gene codes for an enzyme called acid sphingomyelinase. Acid sphingomyelinase is responsible for catalyzing a reaction to break down a phospholipid called sphingomyelin. This phospholipid is usually found in the membrane of your cells. 

In NPD type A and B, mutations in the SMPD1 gene mean that the amount of acid sphingomyelinase is very low or completely absent. As a result, sphingomyelin builds up inside structures called lysosomes.

Type C

Niemann-Pick type C (NPC) is the most common type of NPD. It  affects approximately 1 in 150,000 people of the global population; however, it has been estimated to affect up to 3 million people in the USA alone.^1,4 It is recorded in more people of French-Acadian descent.¹

NPC can appear at any age. In general, people who are diagnosed later in life are more likely to be able to live into adulthood. It has been estimated that this can be up to 25 years old for some people.⁴ Despite this, a case of asymptomatic NPC has been reported in a woman who was 66 years old.⁵ Whilst this is quite rare, it can reflect the difficulty of receiving a correct NPC diagnosis.

Type C is caused by mutations in the Niemann-Pick type C 1 (NPC1) or 2 (NPC2) genes. These genes code for proteins that are needed to transport cholesterol through cells in structures known as lysosomes and endosomes.^2,6

Cholesterol is an important molecule that is used for various purposes, such as maintaining the cell membrane and the formation of steroid hormones.⁷ Therefore, people with NPC can experience a variety of symptoms.

Challenges of living with Niemann-Pick disease

People with Niemann-Pick disease have a low life expectancy, as their symptoms become worse over time. This can be especially challenging for those who are diagnosed later in life.

In Lara Avery’s ‘The Memory Book’, Samantha is diagnosed with Niemann-Pick type C (NPC). Before she is diagnosed, she is described as being an intelligent student who dreams of becoming a lawyer and living in her own apartment in New York City. During an important debate match, Samantha has a sudden moment of memory loss. She feels like she is unable to speak and becomes very distressed. Her memory loss becomes worse and more frequent throughout the book.

Learning that you have a life-altering disease will be a shock. You may be diagnosed after experiencing some unusual symptoms, such as sudden pains or behavior changes and memory loss, like Samantha. You might have to eventually stop doing things that you could normally do before, such as going to school or getting yourself out of bed. Like Samantha, you may have to change your future goals. You will also have to have your symptoms monitored regularly by doctors and other healthcare professionals.

Carers of children with Niemann-Pick

Having your child diagnosed with NPD is not easy to face. They may become increasingly more dependent on your care as their symptoms worsen. There are many charities that are dedicated to providing support to people with Niemann-Pick and their families. Niemann Pick UK (NPUK) and the National Niemann Pick Disease Foundation have useful web pages that explain how they could support you.

Improving quality of life for people with Niemann-Pick disease 

Medication

Clinical trials and research are ongoing to find new treatments for Niemann-Pick. There are some drug treatments available which can help to slow down the progression of the disease. 

Olipudase alfa

NPD types A and B can be treated by increasing the amount of active acid sphingomyelinase. Currently a drug called olipudase alfa, sold as Xenopozyme, is used to treat this enzyme deficiency. Olipudase alfa acts like the enzyme, acid sphingomyelinase, normally would. It is injected into the bloodstream.Olipudase alfa has been effective at increasing blood platelet levels as well as reducing organ enlargement.⁸ Unfortunately, it has no effect on the neurological symptoms of NPD. 

Miglustat

For people with NPC, miglustat may be used to reduce the rate of disease progression.  Miglustat is prescribed to people with mild neurological symptoms. It is taken orally. Long term, miglustat treatment has shown to reduce the death of nerve cells in the brain.⁹ This means that it can help to slow changes in learning and memory, as well as movement.

Arimoclomol

Sold as Miplyffa, arimoclomol was recently approved by the US Food and Drug Administration (FDA) for NPC treatment when prescribed with miglustat. It has been shown to reduce the severity of NPC.¹⁰

Levacetylleucine

The FDA recently approved levacetylleucine (which is sold as Aqneursa) as a standalone treatment for NPC. In a 12-week trial period, levacetylleucine was shown to reduce cognitive decline when compared to those taking a placebo.¹¹ It was reported to have minimal side effects, however, its long term effects have not yet been studied.   

Support therapy

Support therapies are designed to help you live with your symptoms. The support you receive will be tailored towards the symptoms you present.

You may be asked to control your diet to reduce the amounts of fatty acids available in your bloodstream. This may slow down the impacts of NPD, especially on your liver. This will be managed by registered dietitians.

Reduced muscle control is also a common symptom of NPD. If this affects your ability to walk and move around, you will receive physiotherapy and occupational therapy. These therapists are trained to help you practice moving around in a safe environment and increase your independence as much as possible.

In other cases, the muscles affected can be in your face. It is common to have speech and swallowing difficulties if you have NPD. Speech and language therapy aims to assess your abilities and determine any changes you may need to help you swallow food and drink.

Mental health

As well as your physical symptoms, your mental health may suffer. These can result due to neurological damage from the disease itself or because of the stress of dealing with NPD and other symptoms. Depression, paranoia, and schizophrenia are examples of the challenges you may experience alongside cognitive decline. 

Your mental health can make it more difficult for you to thrive. However, there is a range of support available for these conditions. These can include:

• Talking therapies with a registered mental health professional 
• Creative therapies, such as art therapy
• Alternative therapy options, such as animal-assisted therapy. Hydrotherapy may also be a good option as it can also help with motor issues

In some cases, you may be prescribed medication to assist you with your mental health. What you are prescribed depends on your symptoms. Please note that only a registered health professional can prescribe psychiatric medication.

Summary

Being diagnosed with Niemann-Pick disease can be very scary. However, it does not mean that you have to suffer alone. By noticing symptoms early on you can receive the support you need sooner. This can help you improve your outcomes as well as your quality of life. Remember that you can access support whenever you need it.