What's Niemann-Pick disease type C?
Niemann-Pick disease type C (NPC) is a rare, autosomal recessive, neurovisceral lysosomal storage disorder caused by biallelic variants in NPC1 (about 95% of cases) or NPC2. Unlike the enzyme-deficiency lysosomal diseases, NPC is a lipid-trafficking defect: the cell cannot move cholesterol and other lipids out of late endosomes and lysosomes, so unesterified cholesterol and glycosphingolipids accumulate. It presents across infantile, juvenile, and adult forms with progressive neurological decline plus visceral signs. This is a distinct entity from Niemann-Pick types A and B (ASMD), which are caused by deficiency of the enzyme acid sphingomyelinase (SMPD1).
| Also indexed as | ORPHA:646, MONDO:0018982 |
|---|---|
| Features mapped | 17 |
| Treatments mapped | 3 |
| Published sources | 12 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Vertical supranuclear gaze palsy
Vertical supranuclear gaze palsy, difficulty moving the eyes up and down on command, is a hallmark of Niemann-Pick type C and is often an early clue, though it is easily overlooked.
Ataxia
Ataxia (problems with balance and coordination) is a common and progressive neurological feature.
Dementia
Progressive loss of thinking and memory (dementia) is among the neurological manifestations of Niemann-Pick disease type C as the disease advances.
Dysarthria
Dysarthria (slurred or effortful speech) is common, alongside swallowing difficulty, as the neurological disease progresses.
Global developmental delay
Developmental delay, where a child is slower to reach milestones than expected, is a common neurological finding in Niemann-Pick disease type C, especially in forms that begin in childhood.
Dystonia
Dystonia, involuntary muscle contractions causing abnormal postures or movements, is part of the movement-disorder picture in Niemann-Pick type C.
Gait ataxia
Unsteady, uncoordinated walking (gait ataxia) is one of the hallmark neurological signs of Niemann-Pick disease type C, reflecting involvement of the cerebellum.
Cataplexy
Cataplexy, a sudden brief loss of muscle tone (often gelastic, triggered by laughter), occurs in a notable minority of patients and links the condition to the brain's orexin system.
Seizure
Seizures can occur in Niemann-Pick disease type C as part of its progressive effect on the brain.
Psychosis
Psychosis can be part of Niemann-Pick disease type C, sometimes appearing as a treatment-resistant picture that looks like schizophrenia. It can show up at any age and may be one of the presenting signs that prompts testing for the condition.
Splenomegaly
Enlargement of the spleen (splenomegaly) is a very common visceral sign and may be present from early on, sometimes before neurological symptoms appear.
Prolonged neonatal jaundice
In newborns and infants, Niemann-Pick disease type C can cause long-lasting jaundice from blocked bile flow (cholestatic jaundice), where the skin and eyes stay yellow. This is one of the early signs that can prompt testing for the condition.
Dysphagia
Difficulty swallowing (dysphagia) is a characteristic feature of Niemann-Pick disease type C and tends to worsen over time, raising the risk of choking and aspiration.
Hepatomegaly
An enlarged liver (hepatomegaly) is a common internal-organ finding in Niemann-Pick disease type C. In one group of people with the condition it was present in most patients.
Cognitive impairment
Progressive cognitive impairment and dementia develop as the disease advances, varying with the age at which neurological symptoms begin.
Axial dystonia
Dystonia, sustained involuntary muscle contractions that twist the body or limbs into abnormal postures, is a characteristic movement problem in Niemann-Pick disease type C.
Hepatosplenomegaly
Enlargement of the liver and spleen (hepatosplenomegaly) is a common systemic feature of Niemann-Pick disease type C, sometimes appearing in infancy before neurological signs.
How it is diagnosed
Niemann-Pick disease type C
Diagnosed using: filipin staining of cultured skin fibroblasts.
“Definitive diagnosis is achieved through genetic testing. Filipin staining test was the gold standard in the past.”
Niemann-Pick disease type C
Diagnosed using: NPC1 and NPC2 gene testing.
“Definitive diagnosis is achieved through genetic testing.”
Niemann-Pick disease type C
Diagnosed using: plasma oxysterol and lysosphingolipid biomarker screening.
“Novel lipid biomarkers including N-palmitoyl-O-phosphocholine-serine and oxysterols such as 7-ketocholesterol and cholestane-3β,5α,6β-triol also show diagnostic value.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
miglustat
Miglustat is the established disease-directed medicine for Niemann-Pick disease type C. It has been shown to help delay the worsening of the condition's neurological symptoms; it slows progression rather than curing the disease.
Used to help with: Niemann-Pick disease type C.
“Miglustat, a glucosylceramide synthase (GCS) inhibitor, is the approved therapy in Europe specific to NP-C1 for slowing and preventing the neurological manifestations of NP-C1.”
arimoclomol
Arimoclomol is a medicine approved in the United States for treating Niemann-Pick disease type C, used together with miglustat. In a controlled trial it slowed how quickly the condition progressed.
Used to help with: Niemann-Pick disease type C.
“Arimoclomol and NALL showed significant improvements of neurological symptoms and reasonable safety profiles in phase II/III trials.”
L-acetylleucine
Acetylleucine (also called N-acetyl-L-leucine or levacetylleucine) is a newer therapy granted marketing authorization for Niemann-Pick type C, used to improve neurological symptoms.
Used to help with: Niemann-Pick disease type C.
“L-acetylleucine was recently granted for marketing authorization by European Medicine…”
How to read the evidence labels
Where this comes from
This guide is built from 12 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.