Niemann-Pick disease type C2 (NPC2)

Doctors often first suspect Niemann-Pick type C (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, and changes in learning or thinking. In NPC2, lung disease in a baby who also has a large liver can point doctors toward the diagnosis. 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, a fat called PPCS (also known as lyso-SM-509) and unusual bile acids. 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.

NPC is not on the U.S. federal list of recommended newborn screening conditions. Some states screen newborns for “Niemann-Pick disease,” but that 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, lung care, speech and swallowing therapy, physical and occupational therapy, nutrition, psychology and social work.

Some medicines are approved to treat the brain and nerve problems of NPC. Miglustat is approved for this in several countries, including the European Union, but not in the United States as a stand-alone treatment. In 2024 the US 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. Levacetylleucine was also authorized in the European Union 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. These medicines were studied in NPC as a whole, and because NPC2 is so rare, the evidence specific to NPC2 is limited.

Published reports of a donor bone marrow transplant for NPC2 are very rare. The NPC2 protein is small and can pass from donor cells to the patient’s cells, so a transplant can in theory supply it. In the best-described case, a boy with lung disease had a transplant at 16 months. His lungs briefly improved, then got much worse as the donor cells took hold, and he needed strong immune-suppressing treatment before his lung disease cleared. At age 5 he had no breathing problems and was walking, but his development, especially speech, was still clearly delayed.

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.

Very few people with NPC2 have been described in medical journals. Most NPC2 gene changes found so far are severe. Many babies with NPC2 have serious lung inflammation, and several reported children died young from lung disease. A few NPC2 gene changes are linked to forms that begin later in life. In NPC as a whole, a severe form that starts before or around birth with liver failure usually leads to death before 6 months of age.

Approved NPC medicines treat the brain and nerve symptoms, but none is a cure. Because NPC2 is so rare, there is little evidence on these medicines in NPC2 specifically. Guidelines advise planning early for feeding, such as a feeding tube, and linking families with local palliative (comfort-focused) care over time. No number can say how one child’s illness will go.