Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy
Niemann-Pick disease type C (NPC) - Clinical Profile, Genes & Research | Kisho | Kisho
Niemann-Pick disease type C (NPC) is described in the packet as a complex lipid storage disease mainly characterized by accumulation of unesterified cholesterol in the late endosomal/lysosomal compartment. GeneReviews characterizes it as a slowly progressive lysosomal disorder whose principal manifestations depend on age. Orphanet, GARD and MeSH identifiers are listed in the packet, and the packet records onset categories of antenatal, neonatal and juvenile. The packet's prevalence field gives a category of uncommon with an estimate of 1-9 in 100,000, while GeneReviews cites lower regional estimates. Seven subtypes are listed, covering type C1, type C2 and several onset-defined forms from severe perinatal to adult neurologic onset.
Clinical Presentation
Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.
The packet contains no structured phenotype entries (the phenotype count is 0), so this section draws on the GeneReviews clinical description. GeneReviews states that manifestations in the perinatal period and infancy are predominantly visceral, with hepatosplenomegaly, cholestatic jaundice and, in some instances, pulmonary infiltrates. From late infancy onward, presentation is dominated by neurologic manifestations. The youngest children may present with hypotonia and developmental delay, followed by ataxia, dysarthria, dysphagia and, in some individuals, epileptic seizures, dystonia and gelastic cataplexy. Cognitive impairment may be subtle at first but eventually progressive dementia becomes apparent. Older teenagers and young adults may present predominantly with apparent early-onset dementia or psychiatric manifestations, although GeneReviews notes that detailed examination usually identifies typical neurologic signs.
GeneReviews groups presentations by age of onset: early infantile (under 2 years), late infantile (2 to 6 years), juvenile (6 to 15 years) and adolescent/adult (over 15 years). Vertical supranuclear saccadic palsy, which can progress to vertical supranuclear gaze palsy, is described as almost invariably present in children with neurologic manifestations. Some individuals present with isolated splenomegaly in childhood, and GeneReviews states that many individuals with NPC never have organomegaly. In neonatal presentations, fetal ascites and severe neonatal liver disease with cholestatic jaundice are reported.
Genetic Landscape
Assembled from HGNC gene records, ClinGen gene-disease validity evidence, and ClinVar pathogenic variant data. Validity classifications reflect the strength of published evidence linking each gene to this disease.
The packet's structured gene list (known_genes) and inheritance field (inheritance_patterns) are both empty, so gene-level causes and the structured inheritance pattern are not certified in this packet, and no gene is named here. The packet does not supply a molecular mechanism field. The definition describes accumulation of unesterified cholesterol in the late endosomal/lysosomal compartment.
The GeneReviews chapter included in the packet describes NPC as inherited in an autosomal recessive manner and discusses genotype-phenotype correlations, in which certain variant types and protein domains are reported to be associated with early-infantile disease, and in which specific homozygous variants are reported in particular populations. Because the structured fields are unpopulated, these genetic details are attributed to GeneReviews alone.
Diagnosis
Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.
The packet's diagnostic method fields are not populated, so this section follows the GeneReviews diagnosis chapter. GeneReviews states that NPC is suspected on the basis of age-dependent clinical findings together with preliminary laboratory findings. It describes oxysterol assay as having largely replaced formerly used diagnostic methods and as a robust screening test and diagnostic test, and it notes that bile acids derived from 7-oxocholesterol and from cholestane-3,5,6-triol are also elevated and may serve as markers in neonates and older individuals.
Per GeneReviews, the diagnosis is established in a proband with biallelic pathogenic or likely pathogenic variants identified by molecular genetic testing. Family history is described as consistent with autosomal recessive inheritance, and absence of a known family history does not preclude the diagnosis. GeneReviews states that the absence of organomegaly never eliminates the diagnosis. Its differential diagnosis for neonatal and infantile presentations includes biliary atresia, congenital infections, malignancies, tyrosinemia type I, alpha-1-antitrypsin deficiency, GM1 gangliosidosis, Gaucher disease type 2 and Niemann-Pick disease types A and B. For childhood presentations it lists conditions such as pineal region or midbrain tumors, other dementing illnesses and sleep disorders.
Treatment
Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.
The packet contains no approved_treatments or foundational_therapies fields and no verified FDA records, so the following reflects the GeneReviews management chapter and the orphan drug list. GeneReviews states that no curative therapy for NPC exists. It describes management as including a set of evaluations after diagnosis spanning physical, neurologic, developmental, cognitive, feeding, ophthalmologic, hearing, psychiatric, genetic counseling and family support domains, and a surveillance schedule covering similar domains. GeneReviews notes that revised clinical management guidelines are being developed.
GeneReviews reports that miglustat is approved for management of neurologic manifestations of NPC in several countries but is not currently FDA approved for standalone treatment of NPC in the United States. It reports that arimoclomol is FDA approved for use in combination with miglustat for neurologic manifestations in persons aged 2 years and older, and that levacetylleucine is FDA approved for neurologic manifestations in adults and children weighing 15 kg or more. These approval statements come from GeneReviews rather than from a certified FDA field in the packet. GeneReviews describes miglustat-associated loose stools and flatus. It also lists drug and circumstance cautions, including drugs that cause excessive salivation or exacerbate seizures, alcohol, and drugs that exacerbate ataxia.
The orphan drug list records designations only, which are not approvals. Allopregnanolone (La Jolla Pharmaceutical Company) has WITHDRAWN status. Designated products include a deoxynojirimycin derivative (Azafaros BV), cholesteryl oleate (Meizon Innovation Pty Ltd.), hydroxypropyl-beta-cyclodextrin (Cyclo Therapeutics, Inc.), miglustat (Edenbridge Pharmaceuticals LLC), 2-hydroxypropyl-B-cyclodextrin (Mandos LLC) and an AAV9-hNPC1 vector (NHGRI, NIH).
Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.
The packet has no natural_history field, so prognosis is not certified as a structured element. GeneReviews describes NPC as slowly progressive, with an age-dependent course. It reports that many infants succumb at the early visceral stage, while some survivors are hypotonic and developmentally delayed and others have complete resolution of manifestations before presenting with neurologic disease many years later. In the retrospective study of 34 children with early liver involvement, four died by age six months and cholestasis regressed in all who survived beyond that age. GeneReviews states that the phenotype usually runs true within families, with rare exceptions. For specific genotypes, GeneReviews reports early childhood death in some groups and survival into mid-adulthood in others. No overall life expectancy figure is supplied in the packet.
Research Landscape
Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.
The packet lists two clinical trial records. NCT06985212, titled as a national multicentre natural history study of acid sphingomyelinase deficiency in adults and children, sponsored by Wladimir Mauhin, is recruiting, with a start date of 2025-05-02 and completion date of 2035-04-15; its title refers to a different named condition, so its relevance to NPC is not established by the packet. NCT03655223, Early Check: Expanded Screening in Newborns, sponsored by RTI International, has active-not-recruiting status, with a start date of 2018-10-15 and completion date of 2026-12-31.
GeneReviews reports that uncontrolled clinical studies of intrathecal 2-hydroxypropyl-beta-cyclodextrin suggested amelioration of disease progression, whereas a controlled trial (NCT02534844) did not show a difference between control and intervention groups. The research landscape digest classifies 144 publications, with basic science and preclinical work dominant, and notes gene therapy publications, biomarker publications and recent trial publications, plus 14 case reports and 23 reviews. Patient organizations listed in the packet are the Ara Parseghian Medical Research Foundation and the Hide & Seek Foundation for Lysosomal Disease Research.
Data assembled from 6 of 12 sources · Last updated Nov 4, 2026, 6:53 AM UTC
Diseases are connected by shared genes, phenotypes, therapeutic targets, and MONDO disease hierarchy. The Rare badge reflects Kisho's rarity classification — scored from authoritative sources including OMIM, Orphanet, orphan drug designations, clinical trial activity, and published prevalence data.
With its acquisition of IntraBio, Shionogi will gain ownership over Aqneursa, which could hit peak global sales of $1 billion across its two indications in Niemann-Pick disease type C and ataxia-telangiectasia, according to Jefferies. IntraBio continues to study Aqneursa in other rare diseases, including GM2 gangliosidoses, inherited cerebellar ataxias and CACNA1A-related disorders. The biotech, founded in 2015, is also developing treatments for common disorders like migraine and dementias. Shionogi has moved to acquire commercial-stage IntraBio for $2 billion upfront just weeks after the Texas-based biotech secured an FDA approval in a rare disease for which there are no other treatments. Tristan is BioSpace‘s senior staff writer. Based in Metro Manila, Tristan has more than eight years of experience writing about medicine, biotech and science. Despite a slowdown in Q3, 2026 is still shaping up to be a big year for M&A. Recent standout takeovers include Vertex Pharmaceuticals’ acquisition of Crinetics Pharmaceuticals—a deal originally billed to be worth $10 billion but which has been valued at $8.8 billion by S&P Capital IQ, after taking into account debt and other factors.
With its acquisition of IntraBio, Shionogi will gain ownership over Aqneursa, which could hit peak global sales of $1 billion across its two indications in Niemann-Pick disease type C and ataxia-telangiectasia, according to Jefferies.
Shionogi & Co. agreed to acquire ... approved rare disease drug and a pipeline of neurodegenerative disease programs to its portfolio. Under the terms of the deal, signed Monday, Shionogi's U.S. division — headquartered in New Jersey — will purchase all of IntraBio's shares, absorbing the biotech as a wholly owned subsidiary. The transaction is expected to close between November and December, the company said. Through the acquisition, Shionogi ... Shionogi & Co. agreed to acquire Austin, Texas-based IntraBio for $2 billion, adding an approved rare disease drug and a pipeline of neurodegenerative disease programs to its portfolio. Under the terms of the deal, signed Monday, Shionogi's U.S. division — headquartered in New Jersey — will purchase all of IntraBio's shares, absorbing the biotech as a wholly owned subsidiary. The transaction is expected to close between November and December, the company said. Through the acquisition, Shionogi will take ownership of worldwide rights to Aqneursa (levacetylleucine), encompassing both intellectual property and commercialization rights. The deal extends a rare disease push that Shionogi began when it brought the ALS therapy Radicava into its portfolio in April 2026 by securing worldwide rights to edaravone from Tanabe Pharma. "Bringing Aqneursa to Shionogi after our acquisition of Radicava will deepen our commitment to rare disease communities, expand our capabilities and strengthen our portfolio as we advance future innovation for patients with significant unmet needs," CEO Isao Teshirogi said in a statement. The drug is approved in the U.S. for the treatment of neurological manifestations of Niemann-Pick disease type C, a rare inherited disorder that impairs the movement of cholesterol and other lipids within cells. The U.S. Food and Drug Administration approved Aqneursa for that condition in September 2024 and the European Medicines Agency followed in January 2026. The FDA granted Aqneursa a second approval on September 18, 2026, for the treatment of ataxia in patients with Ataxia-Telangiectasia, a rare progressive neurodegenerative disease that typically begins in early childhood. Shionogi said IntraBio's rare disease capabilities would also support its broader pipeline, which includes clinical programs in Pompe disease, Fragile X $TWTR syndrome, and Jordan's syndrome.
Japanese firm builds its global rare disease portfolio and pipeline with acquisition of US-based IntraBio and lead drug Aqneursa for Niemann-Pick disease Type C.
