What Is Niemann Pick Disease?

Overview

Niemann-Pick disease (NPD) is a rare, inherited metabolic disorder that affects the body's ability to break down fats and cholesterol, which then accumulate in various organs and tissues causing organ damage and dysfunction. 

NPD is caused by mutations in one of several genes that produce enzymes involved in lipid metabolism, and it is classified into four types (NPD types A, B, C, and D) based on the specific gene affected and the severity of the symptoms.

Read on to find out more about the types, symptoms, and treatments of NPD.

Types of niemann pick disease

NPD type A is the most severe form, with symptoms typically appearing within the first few months of life.¹ Affected individuals have little or no activity of the enzyme acid-sphingomyelinase (ASM), which leads to the buildup of a lipid called sphingomyelin in the liver, spleen, lungs, and brain. Symptoms include an enlarged liver and spleen, respiratory problems, and neurological deterioration. This can induce mortality in young children by the age of 2-3.

NPD type B is a milder form, with symptoms ranging from childhood to adulthood.² Individuals with NPD type B have some ASM activity, but not enough to prevent the buildup of sphingomyelin in the liver and spleen. Symptoms include an enlarged liver and spleen, lung infections, and sometimes neurological problems.

NPD type C is not associated with ASM activity - instead, it is caused by mutations in one of two genes (NPC1 or NPC2) involved in the transport of cholesterol and other lipids within cells.³ As a result, lipids accumulate in various organs, including the liver, spleen, brain, and lungs, leading to a wide range of symptoms that can include delayed development, progressive neurological problems, seizures, difficulty swallowing, and lung disease. NPD type C can be further subdivided into several clinical subtypes based on the age of onset and severity of symptoms.

NPD type D is a rare form that is caused by mutations in the gene for the protein SERPINA3, which is involved in the transport of lipids within cells. It is characterised by symptoms that resemble those of NPD type C, but with a later onset and slower progression.

Causes of niemann pick disease

NPD is caused by mutations in one of several genes that produce enzymes or proteins involved in lipid metabolism. These mutations disrupt the normal function of these enzymes and proteins, leading to the buildup of lipids in various organs and tissues. 

NPD is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disease. Carriers of a single mutated gene do not have symptoms of NPD, but can pass the mutation on to their children.

Signs and symptoms of niemann pick disease

The signs and symptoms of NPD can vary depending on the type and severity of the disease, but can include:^3,4

• Enlarged liver and spleen (hepatosplenomegaly)
• Respiratory problems
• Neurological problems, including developmental delay, seizures, and cognitive decline
• Difficulty swallowing (dysphagia)
• Lung disease
• Bone and joint problems
• Blood abnormalities

Management and treatment for Niemann-Pick disease

There is currently no cure for NPD, and treatment focuses on managing the symptoms and complications of the disease. For example, enzyme replacement therapy (ERT) has been approved for NPD types A and B and involves infusing a modified version of the missing enzyme into the bloodstream.⁵ ERT can improve lung function and reduce the size of the liver and spleen, but it does not cross the blood-brain barrier and therefore does not treat the neurological symptoms of NPD. 

Other treatments may include medications to manage seizures or other symptoms, physical therapy to improve mobility, and dietary changes to manage weight and nutritional deficiencies.

Research is ongoing to develop new treatments for NPD, including gene therapy and small molecule drugs that can cross the blood-brain barrier to treat the neurological symptoms. Clinical trials are also underway to test the safety and efficacy of these treatments.

Diagnosis of niemann pick disease

Diagnosis of NPD typically involves a combination of clinical examination, laboratory testing, and genetic testing.^3,4 Doctors may perform imaging studies, such as X-rays or ultrasound scans, to assess the size of the liver and spleen, or a biopsy to examine tissue samples for lipid deposits. Blood and urine tests can also be used to detect abnormalities in lipid metabolism or enzyme activity.

Genetic testing is the most definitive method of diagnosis and can identify the specific genetic mutation responsible for NPD. This can help with predicting the course of the disease and identifying carriers of the mutation in family members.

FAQs

How can I prevent niemann pick disease?

There is currently no way to prevent NPD, as it is an inherited genetic disorder. However, genetic counselling and testing can help individuals understand their risk of having a child with NPD and make informed decisions about family planning.

How common is niemann pick disease?

NPD is a rare disease, with an estimated incidence of 1 in 250,000 to 1 in 500,000 live births. However, the exact prevalence of NPD may be underestimated due to underdiagnosis and misdiagnosis.⁶

Who is at risk of niemann pick disease?

NPD is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disease. Individuals with a family history of NPD or who are carriers of a mutated gene are at increased risk of having a child with NPD.

When should I see a doctor?

If you or your child has symptoms of NPD, such as an enlarged liver or spleen, respiratory problems, or neurological problems, you should see a doctor for evaluation and testing. Early diagnosis and management can improve outcomes and quality of life for individuals with NPD.

Summary

Niemann-Pick disease (NPD) is a rare, inherited metabolic disorder that affects lipid metabolism and leads to the accumulation of lipids in various organs and tissues, often the liver and spleen. NPD is caused by mutations in genes that produce enzymes or proteins involved in lipid metabolism, and is classified into four types based on the specific gene affected and the severity of the symptoms. 

There is currently no cure for NPD, and treatment focuses on managing the symptoms and complications of the disease. Genetic counseling and testing can help individuals understand their risk of having a child with NPD and make informed decisions about family planning. Early diagnosis and management can improve outcomes and quality of life for individuals with NPD.