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Niemann-Pick disease type B
This condition is caused by a fault in the SMPD1 gene, leading to reduced activity of an enzyme critical for fat metabolism. It primarily affects the lungs, liver, spleen, and bone marrow, and does not typically involve the brain.
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Overview
Niemann-Pick disease type B (NPD B) is a rare genetic disorder, part of a group known as lysosomal storage disorders. Lysosomes are compartments within cells that break down waste products and fats. In NPD B, a specific fat called sphingomyelin cannot be broken down properly, leading to its build-up within cells in various tissues and organs [PMID:24075217]. This accumulation causes these organs to enlarge and can affect their normal function.
NPD B primarily affects the liver, spleen, lungs, and bone marrow. Unlike some other forms of Niemann-Pick disease, NPD B generally does not involve the central nervous system, meaning it typically does not cause neurological problems. Symptoms can vary widely among affected individuals, even within the same family, ranging from mild to severe.
Symptoms & clinical features
Symptoms of Niemann-Pick disease type B usually appear in childhood, but they can also manifest during adolescence or adulthood. A common early sign is an enlarged spleen (splenomegaly) and liver (hepatomegaly), which can sometimes be detected during routine medical examinations [PMID:24075217]. This enlargement can lead to abdominal discomfort or a feeling of fullness.
Lung involvement is also common and can result in breathing difficulties, chronic cough, and frequent lung infections. Some individuals may experience blood count abnormalities due to bone marrow involvement, such as a reduced number of platelets (thrombocytopenia), which can lead to easy bruising or bleeding, or a reduced number of white blood cells (leukopenia). Growth delays may also be observed in children with the condition. Bone density can sometimes be affected, leading to weaker bones.
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Affected organs
Niemann-Pick disease type B predominantly affects several key organ systems. The spleen and liver are almost always involved, becoming enlarged due to the accumulation of sphingomyelin. This hepatosplenomegaly is a hallmark feature of the condition.
The lungs are frequently affected, with sphingomyelin build-up leading to interstitial lung disease, which can impair lung function over time. The bone marrow can also be infiltrated, contributing to problems with blood cell production, such as low platelet counts. Other organs that may be affected include the heart, where sphingomyelin deposits can lead to heart problems in some cases, and the skeletal system, which may show reduced bone density.
Risks & severity
The severity of Niemann-Pick disease type B can vary considerably, even among individuals with the same genetic fault. Some people may experience mild symptoms that develop slowly over many years, while others may have more significant health problems that manifest earlier in life [PMID:24075217]. The exact prevalence of NPD B in the UK is not well established, but it is considered a rare disease.
Lifetime risks are difficult to quantify precisely due to the variability of the condition, but progressive organ damage, particularly to the lungs and liver, can lead to serious health complications. While NPD B typically does not affect the brain, the accumulation of sphingomyelin can sometimes lead to an increased risk of cardiovascular disease. Regular monitoring and supportive care are important for managing the progression of the condition.
Genetic causes
Niemann-Pick disease type B is caused by pathogenic variants in the SMPD1 gene. This gene provides instructions for making an enzyme called acid sphingomyelinase (ASM). ASM is located in the lysosomes, the recycling centres of cells, where its job is to break down the fatty substance sphingomyelin into ceramide and phosphocholine [PMID:28798939].
When there are pathogenic variants in the SMPD1 gene, the activity of the ASM enzyme is significantly reduced or completely absent. This leads to an inability to properly break down sphingomyelin, causing it to accumulate in the lysosomes of cells throughout the body. The build-up of sphingomyelin is toxic to cells and disrupts their normal function, leading to the symptoms observed in Niemann-Pick disease type B.
- SMPD1 sphingomyelin phosphodiesterase 1
Inheritance pattern
Niemann-Pick disease type B is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the pathogenic SMPD1 gene variant - one from each parent - to develop the condition. People who inherit only one copy of the variant are called carriers; they typically do not show symptoms of the disease but can pass the variant on to their children.
If both parents are carriers of an SMPD1 gene variant, there is a 1 in 4 (25%) chance with each pregnancy that their child will inherit two copies of the variant and develop Niemann-Pick disease type B. There is also a 2 in 4 (50%) chance that their child will be a carrier, and a 1 in 4 (25%) chance that their child will inherit two unaffected copies of the gene and not be a carrier or have the condition.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
A diagnosis of Niemann-Pick disease type B is often suspected based on clinical signs and symptoms, such as an enlarged liver and spleen, or recurrent respiratory infections. Initial investigations may include imaging studies and blood tests. Confirmation of the diagnosis typically involves laboratory testing to measure the activity of the acid sphingomyelinase (ASM) enzyme, usually in white blood cells or cultured skin cells [PMID:24075217]. Reduced ASM activity indicates NPD B.
Genetic testing for pathogenic variants in the SMPD1 gene is then performed to confirm the diagnosis and identify the specific genetic changes responsible for the condition. In the UK, genetic testing for Niemann-Pick disease is typically accessed through NHS Genomic Medicine Centres following a referral from a specialist clinician. The relevant NHS Genomic Medicine Service (GMS) 'R-code' for Niemann-Pick disease, covering SMPD1, is R440 Inherited metabolic disorders.
Management & lifestyle
Currently, there is no cure for Niemann-Pick disease type B, and management focuses on supportive care to alleviate symptoms and manage complications. This often involves a multidisciplinary team of specialists, including hepatologists, pulmonologists, and haematologists.
Regular monitoring of organ function, particularly the liver, spleen, and lungs, is crucial. Treatments may include oxygen therapy for lung problems, transfusions for blood count abnormalities, and potentially enzyme replacement therapy (ERT) for some forms of Niemann-Pick disease, though its effectiveness specifically for NPD B is still being evaluated. Clinical trials are ongoing to explore new therapeutic approaches. Individuals and families should discuss management strategies with their clinical genetics team and other specialists involved in their care.
UK care pathway
In the UK, individuals suspected of having Niemann-Pick disease type B would typically be referred to a clinical geneticist or a specialist in inherited metabolic disorders. These specialists can evaluate symptoms, arrange for diagnostic testing, and coordinate care with other medical professionals. Genetic testing, which may include analysis of the SMPD1 gene (NHS GMS R-code R440), is generally performed through the NHS Genomic Medicine Service.
Following a diagnosis, individuals and their families will have access to genetic counselling. Genetic counsellors provide information about the condition, its inheritance pattern, and discuss implications for family members. They also offer support and help families navigate the healthcare system.
Frequently asked questions
What is the difference between Niemann-Pick type A and type B?
Both types A and B are caused by problems with the SMPD1 gene, but type A is more severe, appearing in infancy with brain involvement and a rapid decline. Type B typically starts later, affecting the liver, spleen, and lungs, but generally without brain involvement, and has a more variable course.
Can Niemann-Pick disease type B be prevented?
Niemann-Pick disease type B is a genetic condition, meaning it is inherited. It cannot be prevented. For families with a known history, genetic counselling and prenatal testing options may be available to understand the risks for future pregnancies.
Is there a cure for Niemann-Pick disease type B?
Currently, there is no cure for Niemann-Pick disease type B. Treatment focuses on managing symptoms and complications, as well as supporting overall health. Researchers are actively investigating new therapies, including enzyme replacement and gene therapies.
How does Niemann-Pick disease type B affect daily life?
The impact on daily life varies widely depending on the severity of symptoms. Individuals may experience fatigue, breathing difficulties, or discomfort from enlarged organs. Regular medical appointments and treatments are often necessary, which can affect schooling or work. Supportive care aims to improve quality of life.
How is Niemann-Pick disease type B inherited?
It is inherited in an autosomal recessive pattern. This means a child needs to inherit a faulty gene from both parents to develop the condition. If both parents are carriers, there is a 25% chance their child will be affected with each pregnancy.
References
- Kayler LK, Merion RM, Lee S. Long-term survival after liver transplantation in children with metabolic disorders. Pediatric transplantation. 2002. PMID: 12234269
- Adam MP, Bick S, Mirzaa GM. Acid Sphingomyelinase Deficiency. 1993. PMID: 20301544
- Freitas HMP, Mançano AD, Rodrigues RS. Niemann-Pick disease type B: HRCT assessment of pulmonary involvement. Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia. 2017. PMID: 29340494
- Eskes ECB, Sjouke B, Vaz FM. Biochemical and imaging parameters in acid sphingomyelinase deficiency: Potential utility as biomarkers. Molecular genetics and metabolism. 2020. PMID: 32088119
- McGovern MM, Wasserstein MP, Aron A. Ocular manifestations of Niemann-Pick disease type B. Ophthalmology. 2004. PMID: 15234149
- Zhao S, Shi Q, Deng W. Niemann-Pick Disease Type B in Traumatic Splenic Rupture. The American journal of forensic medicine and pathology. 2020. PMID: 32541392
- Gulten ZA, Cetincelik U, Guler A. Evaluation of Patients Diagnosed with Inherited Metabolic Diseases in Adulthood. Sisli Etfal Hastanesi tip bulteni. 2025. PMID: 41573607
- Simpson WL Jr, Mendelson D, Wasserstein MP. Imaging manifestations of Niemann-Pick disease type B. AJR. American journal of roentgenology. 2010. PMID: 20028884