What is Niemann-Pick Disease?

The incidence of Niemann-Pick disease types A and B combined is estimated to be approximately 1 in 250,000 births. However, this number can vary based on ethnic groups and geographic regions. For instance, Niemann-Pick disease Type A is more common among Ashkenazi Jewish populations, with an estimated incidence of about 1 in 40,000 births within this community.
Niemann-Pick disease types A and B are part of a group of lysosomal storage disorders that affect the body's ability to metabolize lipids (fats) properly. These conditions are caused by mutations in the SMPD1 gene, which leads to a deficiency in the enzyme acid sphingomyelinase. This deficiency results in the accumulation of sphingomyelin and other lipids in various organs of the body, leading to the symptoms and complications of the disease. Niemann-Pick disease is inherited in an autosomal recessive manner.

How to diagnose?

Diagnosis of Niemann-Pick disease Types A and B typically involves clinical evaluation, genetic testing to identify SMPD1 mutations, and enzyme assay to measure the activity of acid sphingomyelinase in white blood cells or fibroblasts.
What is the treatment?
Treatment has been supportive, focusing on symptom management, until the introduction of Xenpozyme (olipudase alfa) in August 2022.

Xenpozyme (olipudase alfa), the first enzyme replacement therapy approved specifically for Niemann-Pick disease type B, addresses the enzyme deficiency at the disease's root. Administered bi-weekly via intravenous infusion, Xenpozyme has shown efficacy in reducing spleen and liver size, improving lung function, and normalizing blood lipid levels in clinical trials. This represents a significant advancement in treatment, offering hope for improved quality of life for patients with Niemann-Pick disease type B.

Type A and B (ASMD or Acid Sphingomyelinase Deficiency)

Type A Niemann-Pick Disease

Type A is the more severe form of the condition and primarily affects infants. It is characterized by an enlarged liver and spleen (hepatosplenomegaly), failure to thrive, and severe neurological symptoms. Children with Type A Niemann-Pick disease usually exhibit developmental delay, loss of early motor skills, and eventually severe brain damage, which is usually fatal by early childhood.

Type B Niemann-Pick Disease
Type B is less severe and primarily affects the liver and spleen. Individuals with Type B may not show symptoms until later in childhood or even into adulthood. The hallmark of Type B is also hepatosplenomegaly, but unlike Type A, the central nervous system is not affected. Symptoms may include growth delay and lung disease. Life expectancy for individuals with Type B can vary widely, with many living into adulthood.

500+ Estimated New Cases Worldwide and 16+ in the US each year

Niemann-Pick Type A
Type A is more severe and usually becomes apparent in infancy. Common signs and symptoms include:
  • Cherry-red Spot on the Eye: A distinctive red spot on the retina of the eye, which is a hallmark sign, although not exclusive to Niemann-Pick disease.
  • Failure to Thrive: Infants may not gain weight or grow at the expected rate.
  • Enlarged Liver and Spleen (Hepatosplenomegaly): This is often one of the first signs and can be noticeable within the first few months of life.
  • Developmental Delay: Delays in reaching developmental milestones, such as sitting up or crawling.
  • Neurological Impairment: Progressive deterioration of the nervous system, leading to loss of motor skills and brain function.
  • Feeding Difficulties: Problems with swallowing or feeding can lead to poor nutrition.
  • Frequent Respiratory Infections.
  • Progressive Loss of Hearing and Sight.
Niemann-Pick Type B
Type B is generally less severe than Type A and usually presents in late childhood or adolescence, but it can vary widely. Signs and symptoms of Type B can include:
  • Enlarged Liver and Spleen (Hepatosplenomegaly): This may not be as immediately life-threatening as in Type A.
  • Growth Delay: Children may be shorter than average and experience delayed puberty.
  • Respiratory Problems: Including difficulty breathing and recurrent infections.
  • Fatigue and Weakness
  • Abnormal Blood Counts: Such as low levels of platelets (thrombocytopenia) or low levels of blood cells that fight infection.
  • Lung Disease: Leading to breathing difficulties and potentially oxygen dependence.
  • Increased Risk of Bleeding due to decreased platelet function