Niemann-Pick disease types A and B (ASMD)

ASMD is a lysosomal storage disorder. Lysosomes are the parts of a cell that break down and recycle used material. An enzyme called acid sphingomyelinase breaks down a fat called sphingomyelin. When the enzyme is missing or very low, sphingomyelin builds up in the liver, spleen, lungs and bone marrow, and in some people in the brain.

ASMD is one disease with a wide range of severity. Doctors describe three main forms. Type A (infantile neurovisceral) is the most severe and begins in babies. Type B (chronic visceral) affects the body’s organs but not the brain, and can start in childhood or adulthood. Type A/B (chronic neurovisceral) falls in between, with organ problems and some brain and nerve problems. Many people do not fit neatly into one group.

ASMD is different from Niemann-Pick disease type C, even though they share part of a name. Type C comes from changes in other genes, NPC1 or NPC2, and is treated differently.

ASMD is caused by changes in both copies of the SMPD1 gene, which holds the instructions for the acid sphingomyelinase enzyme.

It is inherited in an autosomal recessive pattern. Each parent usually carries one changed copy. When both parents are carriers, each child has a 1 in 4 chance of having ASMD, a 1 in 2 chance of being a carrier and a 1 in 4 chance of neither.

ASMD is found in people of every background. Some gene changes are more common in certain groups. Among Ashkenazi Jewish people, about 1 in 100 to 1 in 200 are estimated to carry one of three changes linked to type A. It is not caused by anything a parent did, and it is not contagious.

In type A, a baby’s liver and spleen usually become enlarged by about 3 months of age. Development moves forward for a while and then stops, around the level of a 1-year-old. After that, skills are lost. Babies often have feeding problems, vomiting, poor growth, irritability and trouble sleeping. A “cherry-red spot” appears at the back of the eye. Fat buildup in the lungs leads to frequent chest infections.

In type B, the main problems are a large spleen and liver, low platelets that can cause easy bruising or nosebleeds, and lung changes that can cause shortness of breath. Children may grow more slowly. Many people have unhealthy cholesterol levels, and adults may have thinner bones. In some people, liver scarring (fibrosis or cirrhosis) develops, sometimes by the 20s or 30s. Type B does not affect the brain, and some people have few symptoms for years.

In type A/B, people have the organ problems of type B along with brain and nerve problems that start later and move more slowly than in type A. These can include clumsiness, trouble with balance, stiff muscles and learning difficulties.

Doctors may suspect type A in a baby with a large liver and spleen whose development stalls, especially when a cherry-red spot is seen at the back of the eye. In older children and adults, a large spleen, low platelets, lung changes on a chest scan or unusual cholesterol levels can be the first clues. Because ASMD is rare and varies so much, it is often missed or confused with other conditions at first.

A blood test for fat-related markers, such as lyso-sphingomyelin and PPCS, can point toward ASMD. An enzyme test in white blood cells or a dried blood spot shows low acid sphingomyelinase activity. Testing of the SMPD1 gene confirms the diagnosis. The enzyme test cannot reliably tell which form a person has, so doctors watch closely for brain and nerve signs over time. A genetic counselor can explain what the results mean for the family.

Niemann-Pick disease is not on the U.S. federal list of recommended newborn screening conditions. A few states screen newborns for ASMD. Illinois was the first to screen every newborn, in 2015, and a 2025 review listed only Illinois and New Jersey. In April 2026, Wisconsin approved adding ASMD to its newborn screening panel; as of August 2026, the change was still going through the state’s rule-making process.

Olipudase alfa (Xenpozyme) is an enzyme replacement therapy. It gives a lab-made version of the missing enzyme through a vein every 2 weeks. The dose starts low and is raised step by step. It was first approved in Japan in March 2022, in the European Union in June 2022 and in the United States in August 2022. In the European Union it is approved for children and adults with type A/B or type B. In the United States it is approved for the problems outside the brain in children and adults with ASMD, with no type named.

In a trial in adults, olipudase alfa improved lung function and shrank the spleen and liver compared with a placebo after one year. Children in open-label studies also had smaller spleens and livers, better lung function and better growth. The enzyme cannot cross into the brain, so it does not treat the brain and nerve problems of type A or type A/B. Allergic reactions, including a severe reaction called anaphylaxis, can happen, so infusions are given where staff and equipment are ready to treat them.

Supportive care is shared by a team. It can include oxygen for lung disease, feeding support, blood products for serious bleeding, and physical and occupational therapy. Guidelines advise against removing the whole spleen. Care teams usually advise people with an enlarged spleen to avoid contact sports.

Before enzyme therapy, a small number of children had a donor stem cell transplant. Transplants could correct the enzyme level in the blood, improve blood counts and shrink the liver and spleen, and lung disease cleared in some children. But they did not stop brain and nerve problems. One girl with type B had a transplant at age 3. Nerve problems appeared by age 6, and her liver scarring kept getting worse. Transplant risks include graft-versus-host disease, infection, kidney problems and death.

People taking olipudase alfa usually have infusions every two weeks, over the long term. Regular checks follow the liver, spleen, lungs, blood counts, cholesterol, bones and growth. Guidelines advise care at a center with experience in ASMD.

For a baby with type A, care focuses on comfort, feeding and breathing. A feeding tube, help with sleep and irritability, and links with palliative (comfort-focused) care can support the whole family. These are some of the hardest days a family can face, and the care team can help plan for them.

Children and adults with type B often live with tiredness, pain or shortness of breath, and anxiety and low mood are more common. The move from children’s to adult care is planned early. Once the family’s gene changes are known, relatives can be tested, and prenatal testing can be offered in a future pregnancy. A genetic counselor can explain the choices.

A registry donor is not part of the usual care for ASMD today. Enzyme therapy treats the problems outside the brain without a donor.

In the reported transplants, the cells came from brothers who did not have ASMD, from a matched unrelated volunteer and from umbilical cord blood. Brothers and sisters are tested before being considered as donors, because they may also have the condition.

A shortage of registry donors is not the main barrier for this condition. Treatments that reach the brain are the bigger need. Joining a registry still helps the many other patients who are waiting for an unrelated donor.

Outlook depends on the form. Type A usually leads to death by age 3 in untreated children, most often from breathing problems. Enzyme therapy does not reach the brain, so it is not expected to change the brain and nerve course of type A. In the European Union it is not approved for type A.

Many people with type B, and some with type A/B, live into adulthood. Before enzyme therapy, serious problems included lung failure, liver failure and bleeding. In a review of people with the chronic forms who had died or needed a liver transplant, breathing failure and liver failure were the leading causes of death, and people with type A/B tended to die younger than people with type B.

Olipudase alfa has been available only since 2022, so its long-term effect on survival is not yet known. Studies show lasting gains in lung function and organ size over several years of treatment. No figure can say how one person’s illness will go.