Niemann-Pick disease Type A (NPA) and Niemann-Pick disease Type B (NPB) were once thought to be separate diseases, but are now understood to be opposite ends of a spectrum of the same disease. They are both caused by a deficiency of the enzyme acid sphingomyelinase (ASM) and therefore are known as Acid Sphingomyelinase Deficiency (ASMD) Niemann-Pick disease. Many variations exist within this spectrum, in terms of clinical symptoms and rate of progression.
NPB is a very rare inherited lysosomal storage disorder in which harmful quantities of a fatty substance called sphingomyelin build up in the body’s cells and organs. In NPB this build up mainly occurs in the liver, spleen and lungs. Unlike NPA, NPB does not affect the brain and, although growth may be slow, those affected will survive into adulthood with many being able to lead a full and active life. A small number of patients may be described as having A/B variant, falling in the middle of the spectrum and exhibiting neurological problems which may become more apparent over time.
It is inherited when two copies of a faulty gene (a mutation) are passed on to a child. In every pregnancy of a couple who each carry a copy of the faulty Niemann-Pick gene, there is a 1 in 4 chance (25%) that their child will have Niemann-Pick disease. This is known as autosomal recessive inheritance.
The incidence of NPB is estimated as 1 in 250,000 in the general population.
Niemann-Pick disease Type B (NPB) is caused by a severe deficiency of the enzyme acid sphingomyelinase. This is required to break down a fatty substance called sphingomyelin. Failure to break down sphingomyelin causes an accumulation and enlargement of the liver and spleen.
Niemann-Pick disease Type B (NPB) is diagnosed by measuring the level of the enzyme acid sphingomyelinase in the white blood cells. This can be done by testing a small blood sample. The diagnosis is usually confirmed by DNA sequencing to identify mutations.
The enzyme deficiency at the cause of NPB arises from mutations in a gene on chromosome 11.
The first symptoms of Niemann-Pick disease Type B (NPB) are usually an enlarged liver and/or spleen in early childhood.
Symptoms can include:
A progressive enlargement of organs
Poor growth
Susceptibility to respiratory infections
Bleeding problems
Bone pain
Increased stress on the heart
There is usually no neurological involvement in NPB. Most patients will survive into adulthood, but not without experiencing health problems.
An enzyme replacement therapy called olipudase alfa (Xenpozyme) is available in many countries, including Scotland. It is the first disease-specific treatment for the non-neurological symptoms of ASMD Type B. Clinical evidence shows it can improve lung function, reduce enlargement of the liver and spleen, and significantly improve quality of life and life expectancy for many people.
In England and Wales, Xenpozyme is not currently recommended by NICE for routine use on the NHS. Care therefore focuses on best supportive treatment. This includes individualised medications and interventions to manage symptoms affecting the lungs, liver, spleen, blood, and bones, with the aim of improving day-to-day wellbeing and quality of life. NPUK continues to support collaborative campaigns which advocate for wider access to this treatment for people affected by Niemann-Pick diseases in the UK.
Research into further treatment options, including gene therapy and other approaches, is ongoing.
Specialist care is essential. Anyone affected by Niemann-Pick disease in the UK should be referred to a designated specialist centre for diagnosis, monitoring, and management.
For the most up-to-date information on treatments, clinical trials, or support, please contact the Niemann-Pick UK Care & Support team.