Niemann-Pick disease type C1 (NPC1)

Niemann-Pick disease type C (NPC) is a lysosomal disorder. Lysosomes are the parts of a cell that break down and recycle used material. Two proteins, NPC1 and NPC2, help move cholesterol and other fats out of them. When either one does not work, fats get trapped inside cells and slowly damage the brain, liver and spleen.

NPC1 disease is the form caused by the NPC1 protein. At least 95 of every 100 people with NPC have this form. The illness can begin at almost any age, from before birth to adulthood. Doctors group it by the age when brain and nerve signs first appear, because that age helps predict how it will progress.

NPC is different from Niemann-Pick types A and B, which are now called acid sphingomyelinase deficiency (ASMD). Those come from a different gene and a missing enzyme.

NPC1 disease is caused by changes in both copies of the NPC1 gene, which holds the instructions for the NPC1 protein.

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 being affected. Carriers can sometimes show some signs or test changes, so results are best explained by a genetic counselor.

It is not caused by anything a parent did, and it is not contagious.

Around birth and in infancy, NPC often shows first in the liver and spleen, with jaundice that lasts for weeks and an enlarged liver and spleen. Some babies have lung disease. A rare severe form that starts before or around birth, with liver failure, usually leads to death before 6 months of age. In other babies, the liver problems settle, and brain and nerve signs appear years later.

When the illness begins in childhood, brain and nerve problems lead. These can include clumsiness and falls, trouble moving the eyes up and down (vertical supranuclear gaze palsy), unclear speech, trouble swallowing, seizures and sudden loss of muscle tone with laughter (gelastic cataplexy). Hearing loss can happen. Learning and thinking skills slowly decline.

When it begins in the teen or adult years, it usually moves more slowly. Memory and thinking problems and mental health symptoms may come first. Some people with NPC also develop bowel inflammation like Crohn’s disease. Swallowing problems can lead to chest infections, which are a common serious complication.

Doctors often first suspect NPC in a baby with jaundice that lasts for weeks and a large liver and spleen. In older children and adults, the clues are usually clumsiness, trouble moving the eyes up and down, sudden loss of muscle tone with laughter, or changes in learning, thinking or mood. A genetic counselor can explain what the results mean for the family.

The first step is often a blood test for markers (biomarkers) that build up in NPC. These include cholesterol breakdown products called oxysterols and a fat called PPCS (also known as lyso-SM-509). These tests make NPC very likely, but a genetic test is needed to confirm it. Testing the NPC1 and NPC2 genes confirms the diagnosis and shows which form it is. When gene results are unclear, a skin-cell test called filipin staining can help.

Niemann-Pick disease is not on the U.S. federal list of recommended newborn screening conditions. Where newborns are screened for “Niemann-Pick disease,” the test looks for the enzyme missing in types A and B, not type C. Because NPC is rare and its early signs are not specific, diagnosis can take a long time. When symptoms start in adulthood, a delay of five years or more is common.

There is no cure. Care is shared by a team that can include neurology, speech and swallowing therapy, physical and occupational therapy, nutrition, psychology, social work and genetics.

Three medicines treat the brain and nerve problems of NPC. Miglustat is approved for this in the European Union and several other countries, but not in the United States as a stand-alone treatment. In September 2024 the United States approved arimoclomol (Miplyffa), used together with miglustat for people aged 2 and older, and levacetylleucine (Aqneursa), for adults and children who weigh at least 15 kg. The European Union authorized levacetylleucine in January 2026 for people aged 6 and older who weigh at least 20 kg, with miglustat or alone when miglustat is not tolerated. In July 2026 the European Medicines Agency recommended against approving arimoclomol, and the company asked for a re-examination, which was still under way in September 2026. International guidelines suggest considering these medicines, and combinations of them, for people with NPC. None is a cure.

A sugar compound called cyclodextrin, given into the spinal fluid or a vein, is being tested in clinical trials. Gene-based therapies are also being studied.

A donor stem cell transplant is not part of care for NPC1. In a 1999 report, a girl with NPC had a bone marrow transplant from her matched brother at age 2½. Her liver, spleen and lungs improved, but her brain and nerve problems kept getting worse. Some newborns with liver failure have had a liver transplant, often before NPC was diagnosed. A liver transplant replaces the organ, not the blood-forming cells. In a review of nine children with NPC who had a liver transplant, most for liver failure as newborns, all survived early infancy, but brain and nerve problems later appeared in 4 of the 7 still alive.

People with NPC need regular follow-up with several specialists to watch for new problems and adjust support. Miglustat often causes diarrhea, gas and weight loss, so people taking it have check-ins for side effects and diet changes.

As swallowing gets harder, feeding support becomes important to keep eating safe and prevent chest infections. Guidelines suggest talking about a feeding tube early, before it is urgently needed. Alcohol and some medicines can make balance or seizures worse, so the care team reviews all medicines.

Most children whose illness starts in the preschool or school years are expected to reach adulthood with complex needs, and the move to adult care is planned early. Family support, psychology, social work and palliative (comfort-focused) care help families plan and cope. Once the family’s gene changes are known, brothers and sisters can be tested, so any who are affected can start treatment early. Testing of children who have no symptoms is decided case by case, and some places do not allow it.

A registry donor is not part of care for NPC1 disease. No current guideline recommends a donor stem cell transplant for it.

In a 1999 report of one child with NPC who had a bone marrow transplant, the cells came from her matched brother, and the transplant did not stop brain and nerve decline. Liver transplants for newborn liver failure use a donated liver, not blood-forming stem cells.

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

NPC covers a wide range, from a fast-moving illness around birth to a slow, long-term illness that begins in adulthood. Doctors group it by the age when brain and nerve signs first appear, because that age is linked with how severe it will be and how long people live. Life spans in NPC range from a few days to many decades.

A severe form that starts before or around birth with liver failure usually leads to death before 6 months of age. When brain and nerve signs begin in childhood, death from a chest infection caused by swallowing problems usually happens in the late teens or 20s. When signs begin in the teen or adult years, the illness moves more slowly and people live longer.

Approved NPC medicines treat the brain and nerve symptoms, but none is a cure. Evidence for miglustat in babies whose nerve signs start before age 2 is limited. Guidelines advise planning early for feeding and linking families with palliative (comfort-focused) care over time. No number can say how one person’s illness will go.