Materiały źródłowe

• #1 Niemann-Pick Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK556129/

  Niemann-Pick disease (NPD) types A and B affect 1 in 250,000 individuals. The prevalence is high in Ashkenazi Jewish descent, where it affects 1 in 40,000 individuals. NPD type C affects 1 in 150,000 persons. Type C is more prevalent in French-Acadian descent in Nova Scotia. […] Niemann-Pick disease is an autosomal recessive (AR) disease, which means both the parents must be affected or carriers of the genes for the disease to pass on to their children. Carrier persons of an AR disease do not show signs and symptoms of the disease, but they can pass the defective gene to the next generation. So if both the parents are carriers, each pregnancy has a 25% chance of producing a child with the disease. Parental counseling should be done, and genetic testing should be offered to families who may be carriers of the disease.

• #2 Niemann-Pick disease: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/niemann-pick-disease/

  Niemann-Pick disease types A and B is estimated to affect 1 in 250,000 individuals. Niemann-Pick disease type A occurs more frequently among individuals of Ashkenazi (eastern and central European) Jewish descent than in the general population. The incidence within the Ashkenazi population is approximately 1 in 40,000 individuals. […] Combined, Niemann-Pick disease types C1 and C2 are estimated to affect 1 in 150,000 individuals; however, type C1 is by far the more common type, accounting for 95 percent of cases. The disease occurs more frequently in people of French-Acadian descent in Nova Scotia. In Nova Scotia, a population of affected French-Acadians were previously designated as having Niemann-Pick disease type D, however, it was shown that these individuals have mutations in the gene associated with Niemann-Pick disease type C1.

• #3 Niemann-Pick Disease | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/25882

  Niemann-Pick disease (NPD) types A and B affect 1 in 250,000 individuals. The prevalence is high in Ashkenazi Jewish descent, where it affects 1 in 40,000 individuals. NPD type C affects 1 in 150,000 persons. Type C is more prevalent in French-Acadian descent in Nova Scotia.[4] […] Niemann-Pick disease is an autosomal recessive (AR) disease, which means both the parents must be affected or carriers of the genes for the disease to pass on to their children. Carrier persons of an AR disease do not show signs and symptoms of the disease, but they can pass the defective gene to the next generation. So if both the parents are carriers, each pregnancy has a 25% chance of producing a child with the disease. Parental counseling should be done, and genetic testing should be offered to families who may be carriers of the disease.

• #4 Niemann-Pick Disease

  https://lysosomalcenter.org/index.php/for-patients/disorders/niemann-pick-disease

  Incidence The incidence of Niemann-Pick disease types A and B combined is estimated to be approximately 1 in 250,000 births. However, this number can vary based on ethnic groups and geographic regions. For instance, Niemann-Pick disease Type A is more common among Ashkenazi Jewish populations, with an estimated incidence of about 1 in 40,000 births within this community. […] 500+ Estimated New Cases Worldwide and 16+ in the US each year

• #5 Newborn Screening Program – Niemann-Pick Disease

  http://www.idph.state.il.us/healthwellness/fs/niemann_pick.htm

  Niemann-Pick disease is an inherited metabolic disorder in which harmful amounts of a sphingolipid called sphingomyelin accumulate within lysosomes of cells. […] The incidence of types A and B combined in the general population is estimated to be one in 250,000. Niemann-Pick disease type A is seen with a higher frequency in the Ashkenazi Jewish population (one in 40,000 births). […] Statewide screening of newborns for lysosomal storage disorders is scheduled to begin in 2014.

• #6 Sphingomyelinase Deficiency: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/951564-overview

  Niemann-Pick disease (NPD) is a rare disorder that occurs in persons of all races. Frequency and distribution of mutations are variable in different ethnic groups and even between different families in the same ethnic groups. […] NPD type A is more common in persons of Ashkenazi Jewish descent. Guidelines for carrier screening for genetic disorders in this population have been established. […] NPD type B occurs worldwide but is more common in the Maghreb region of North Africa, in Saudi Arabia, and in individuals of Turkish descent. NPD type B has various phenotypes, and they are found commonly in Arab, Turkish, and Portuguese populations. In North African patients with NPD type B who originated from Maghreb region, the delta-R608 mutation accounts for almost 90% of mutant alleles. […] NPD types A and B are autosomal recessive disorders, equally affecting males and females. […] Patients with NPD type A disease develop symptoms as early as age 3 months. NPD type B has a variable age of presentation but frequently appears early in childhood, when hepatosplenomegaly is detected and symptoms of lung involvement may occur.

• #7

  https://www.omim.org/entry/607616

  A number sign (#) is used with this entry because Niemann-Pick disease type B, known as the 'visceral’ form, is caused by homozygous or compound heterozygous mutation in the sphingomyelin phosphodiesterase-1 gene (SMPD1; 607608), which encodes acid sphingomyelinase (ASM), on chromosome 11p15. […] Simonaro et al. (2002) collected demographic and/or mutation information on a worldwide sample of 394 patients with type B Niemann-Pick disease. They found that the disorder is panethnic, with the highest incidence occurring in individuals of Turkish, Arab, and North African descent. Only 5 of the 394 patients were Ashkenazi Jewish, revealing that, unlike the type A form of Niemann-Pick disease, type B does not occur frequently within this population. Mutation analysis of the SMPD1 gene was performed on 228 patients and several novel 'common’ mutations were found. The previously reported arg608-to-del mutation (607608.0002) occurred in approximately 12% of the alleles studied. Overall, a total of 45 novel mutations were found, and several new genotype/phenotype correlations were identified.

• #8 Consensus clinical management guidelines for Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0785-7

  Niemann-Pick disease type C (NPC) is a rare genetic disease whose clinical spectrum ranges from a fatal antenatal disorder to an adult-onset chronic neurodegenerative disease. The rarity of the disease and the scarcity of expertise translate into misdiagnosis, delayed diagnosis and barriers to adequate care. […] NPC has an estimated incidence of ~1: 100,000 and the rarity of the disease translate into misdiagnosis, delayed diagnosis and barriers to good care. […] NPC disease is rare, with an estimated incidence of 1 case per 100,000 live births. The disease is pan-ethnic, with at least 95% of all disease due to mutations in the NPC1 gene and the remainder in the NPC2 gene. […] Retrospective national expert centre based studies from Australia, the Netherlands, the UK, Portugal, Czech Republic, France and United Arab Emirates have reported an annual incidence varying between 0.25 and 2.20 per 100,000 live births. […] In addition, owing to better awareness and improved diagnostic methods, a significantly higher proportion of adult-onset cases have been diagnosed during the past 5 years, therefore a recalculation would likely approach a figure slightly higher than 1/100,000.

• #9 Niemann-Pick Disease Type C (NPC) – IntraBio

  https://intrabio.com/disease-information/niemannpickdiseasetypec/

  Niemann-Pick disease Type C (NPC) is a rare genetic disorder, occurring in approximately 1 in 100,000 live births. […] NPC is a serious, debilitating, progressive, neurodegenerative condition. […] The International Niemann Pick Disease Alliance (INPDA) is a global network of non-profit organizations, supporting persons affected by Niemann Pick diseases (NPD). Currently, there are member organizations from 19 countries.

• #10 Niemann-Pick disease type C | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-5-16

  Niemann-Pick C disease (NP-C) is a neurovisceral atypical lysosomal lipid storage disorder with an estimated minimal incidence of 1/120 000 live births. […] Estimates of birth prevalence ranging between 0.66 and 0.83 per 100,000 were proposed for France, the UK and Germany based on diagnoses made in the laboratory of the author over the period 1988-2002. […] For this review, an updated incidence of 0.82/100,000 was calculated for France, considering the total number of cases (n = 63) diagnosed for French hospitals during the 2000-2009 period vs. the number of births during the same period, a possibly more appropriate way of calculation. […] Including prenatal cases from terminated pregnancies during the same period (n = 11) increased the incidence to 0.96 per 100,000. […] The wide clinical spectrum of NP-C was not recognized until the early 1990s, especially regarding rapidly fatal infantile cases, and no specific laboratory testing was available until the mid 1980s. […] Most families (about 95%) belong to the NP-C1 group.

• #11 Estimating the prevalence of Niemann-Pick disease type C (NPC) in the United States – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34304992/

  Niemann-Pick Disease Type C (NPC) is an ultra-rare progressive neurodegenerative disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes that lead to premature death, with most individuals dying between 10 and 25 years of age. […] Currently, there are no approved treatments for NPC in the United States; miglustat, an FDA-approved treatment for Gaucher disease, is used off-label for NPC and GM1 gangliosidosis. […] A total of 308 million unique individuals were represented in the database. Of these, 294 individuals had an NPC diagnosis, yielding an identified NPC prevalence of 0.95 per million people in the United States. […] Based on the published literature, there are an estimated 42 new NPC cases per year. Applying this number to the distribution of NPC type (based on age of neurologic symptom onset) and corresponding mortality estimates generates an estimated 943 prevalent cases of NPC, or 2.9 cases of NPC per million people in the United States.

• #12 Researchers Look at NPC Type C Prevalence in the United States

  https://www.ajmc.com/view/researchers-look-at-npc-type-c-prevalence-in-the-united-states

  Niemann-Pick Disease Type C (NPC), an ultra-rare, progressive neurodegenerative disease, is heterogeneous and is often misdiagnosed or undiagnosed. […] A recent study aimed to get a fuller picture of the prevalence of Niemann-Pick Disease Type C (NPC), an ultra-rare, progressive neurodegenerative disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes. […] Using claims data, researchers sought to estimate the number of people in the United States who fell into 3 categories: Those diagnosed with an NPC diagnosis, Those diagnosed with an NPC diagnosis and/or are treated off-label with miglustat for NPC, Those likely to have NPC. […] To determine the third point of the study, published NPC incidence (1 per 89,000 live births) and expected mortality estimates were applied to the 2018 United States birth rate (11.6 per 1000) and population size (326.7 million).

• #13 Researchers Look at NPC Type C Prevalence in the United States

  https://www.ajmc.com/view/researchers-look-at-npc-type-c-prevalence-in-the-united-states

  For this study, 308 million unique individuals were represented in the Symphony IDV; of these, 294 individuals had an NPC diagnosis, yielding an identified NPC prevalence of 0.95 per million people. […] Researchers also found that 305 individuals were diagnosed with NPC and/or were treated with miglustat without having a diagnosis for either Gaucher or GM1 gangliosidosis, yielding an NPC diagnosed or treated prevalence of 0.99 per million people. […] Based on the published literature, there are an estimated 42 new NPC cases per year. Applying this number to the distribution of NPC type (based on age of neurologic symptom onset) and corresponding mortality estimates generates an estimated 943 prevalent cases of NPC, or 2.9 cases of NPC per million people in the United States. […] The authors said to their knowledge it is the first published analysis of NPC US prevalence.

• #14

  https://omim.org/entry/257220

  Niemann-Pick disease type C has a highly variable clinical phenotype. […] Incidence of 1 in 150,000 live births in the general population. […] Incidence of 1% in Yarmouth County, Nova Scotia. […] Estimated carrier frequency of 10-25% in Yarmouth County, Nova Scotia. […] Greer et al. (1997) noted that Yarmouth County in Nova Scotia appears to have the world’s highest incidence of Niemann-Pick type II disease (encompassing types C and D). […] The frequency of affected children in 1 region of the county was said to be about 1% and the frequency of heterozygous carriers was estimated to be 10 to 26% (Winsor and Welch, 1978). […] Using diagnosis coding information from an administrative database that collates billing-related data from pharmacies and medical facilities, Burton et al. (2021) estimated a prevalence of NPC in the United States of 0.99 per million. […] However, when the NPC prevalence in the United States was calculated based on the number of new cases published in the literature per year, the prevalence was estimated at 2.9 cases per million. […] Burton et al. (2021) concluded that NPC is underdiagnosed in the United States.

• #15 Estimated prevalence of Niemann–Pick type C disease in Quebec | Scientific Reports

  https://www.nature.com/articles/s41598-021-01966-0

  NiemannPick type C (NP-C) disease is an autosomal recessive disease caused by variants in the NPC1 or NPC2 genes. The prevalence varies from 0.35 to 2.2 per 100,000 births depending on the country. The estimated prevalence calculated using those two variants is 0.61:100,000 births. This study represents the first estimate of NP-C in Quebec. The estimated prevalence for NP-C is likely underestimated due to misdiagnosis or missed cases. The prevalence of the disease is variable worldwide due to population differences, diagnostic awareness and diagnostic methodology. Some populations may also have higher disease prevalence because of a founder effect, leading some rare variants to become more frequent. Among the French-Canadian population, we also observe regional founder effects such as in the Saguenay and Gaspesia regions. A founder effect was previously reported in Canada for NiemannPick disease. The prevalence of NP-C for 100,000 live births is 0.47 in Australia, 0.91 in Czech Republic, 2.2 in Northern Portugal, 0.35 in the Netherlands, 0.82 for France, 0.78 for the United Kingdom and 1.12 for the United States of America (USA). By combining these different prevalences, we obtain an average of 0.95 cases per 100,000 births. As there is no registry of NP-C cases in Quebec and it is impossible to measure the prevalence using the classical method, we used the HardyWeinberg equation. Our prevalence estimate based on the two pathogenic variants found in the CaG cohort is 0.51 case every year or 0.61 case per 100,000 births. It would suggest that NP-C could be underdiagnosed clinically in the Quebec population. It is also important to ensure that all NP-C cases are properly diagnosed in order to start treatment as soon as possible.

• #16 Estimating the prevalence of Niemann-Pick disease type C (NPC) in the United States – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34304992/

  NPC is an ultra-rare, progressive neurodegenerative disease with approximately 1 per million people in the United States diagnosed with or treated off-label for NPC. Given that NPC is often misdiagnosed or undiagnosed, the estimated prevalence from the epidemiology calculations (2.9 per million) approximates the number of NPC cases if disease awareness, screening and diagnosis efforts were enhanced.

• #17 Orphanet: Niemann-Pick disease type C

  https://www.orpha.net/en/disease/detail/646

  Prevalence at birth of Niemann-Pick disease type C (NPDC) ranges between 1/45,000-286,000 worldwide. […] NPDC is an autosomal recessive disease. Genetic counseling should be offered to at-risk couples informing them that there is a 25% risk of having an affected child at each pregnancy.

• #18 Niemann-Pick disease type C | MedLink Neurology

  https://www.medlink.com/articles/niemann-pick-disease-type-c

  The disease shows autosomal recessive inheritance and is panethnic. […] Its minimal incidence at birth, calculated from diagnosed patients, is estimated to be about 1 in 100,000. […] In Western Europe, the minimal incidence, estimated earlier to be 1 in 120,000 live births, appears closer to at least 1 in 100,000. […] The population prevalence is estimated to be approximately 1 to 1.5 in 1.106. […] The most common NPC1 variants differ according to the geographical or ethnic origin of the patients. […] The frequency of families with NPC2 mutations varies greatly between countries. A significant number have been described from North Africa, Turkey, and Italy.

• #19 Niemann-Pick disease type C2 | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/niemann-pick-disease-type-c2/

  The exact incidence of Niemann-Pick Disease Type C2 is unknown. It is estimated that Niemann-Pick disease type C affects 1 in 150,000 individuals, with approximately 4% of these cases attributed to mutations in the NPC2 gene. […] The National Niemann-Pick Disease Foundation is a non-profit organization that promotes research into all forms of Niemann-Pick disease and supports patients and their families. […] The Ara Parseghian Medical Research Foundation is a non-profit focusing on raising funds for research into Niemann-Pick disease type C. […] NORD is a patient advocacy organization dedicated to individuals with rare diseases and the organizations that serve them.

• #20 Advancing diagnosis and treatment of Niemann-Pick C disease through biomarker discovery

  https://www.explorationpub.com/Journals/ent/Article/100412

  Niemann-Pick C disease is a rare neurodegenerative, lysosomal storage disease caused by accumulation of unesterified cholesterol. […] The disorder has a clinical incidence of 1/100,000-1/120,000 live births. […] Analysis of whole exome sequence databases predicted an incidence rate of approximately 1/90,000 in close agreement with the clinical data. […] Diagnosis of NPC is challenging due to the rarity of the disorder, the heterogeneity of disease onset and presentation, its non-specific early symptoms, and the complexity of the laboratory testing. […] Consequently, diagnosis is typically delayed 4-5 years for the late-infantile and juvenile forms of the disease, during which time opportunities for early intervention are lost. […] The discovery of blood-based diagnostics and dissemination of rapid, sensitive and specific clinical assays have lowered the barrier for testing and accelerated diagnosis.

• #21 Advancing diagnosis and treatment of Niemann-Pick C disease through biomarker discovery

  https://www.explorationpub.com/Journals/ent/Article/100412

  The only approved drug for treatment of NPC is the glycosphingolipid synthesis inhibitor miglustat. […] At present drug treatment options for NPC are limited. […] The discovery of NPC-specific blood-based biomarkers and their rapid dissemination over the past decade into clinical laboratories have transformed the approach to disease diagnosis. […] The circulating biomarkers most widely used in clinical laboratories—C-triol, TCG and PPCS—all have high sensitivity for identifying NPC disease. […] However, in contrast to C-triol and PPCS, TCG has significant advantages with respect to sample handling and stability and offers higher specificity for discrimination between carriers and NPC patients. […] For these reasons, the plasma TCG assay is recommended as the first-line diagnostic.

• #22 Niemann-Pick Disease Type C: Symptoms, Causes, Treatment

  https://www.healthline.com/health/niemann-pick-disease-type-c

  NPD type C affects about 1 in 150,000 people and is most common in French-Acadian people in Nova Scotia. But it can occur in people of any ethnic background. […] NPD type C can onset at any age. Its important to get medical attention if you notice any cognitive changes or unexplained changes in movement in you or your child. […] The main diagnostic test for NPD type C is now genetic testing for biomarkers, such as: oxysterols, lysosphingolipids, bile acids. […] Currently, NPD type C has no cure, and treatment is largely supportive. People with the disease generally have a better outlook when symptoms develop when theyre at an older age.

• #23 High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets | Genetics in Medicine

  https://www.nature.com/articles/gim201525

  The current diagnosis of NPC is based on filipin staining of unesterified cholesterol in cultured fibroblasts or molecular testing. […] A sensitive blood-based diagnostic test, which detects elevated oxysterols, was recently developed; this test could be used to screen potential patients economically and rapidly. […] Our data indicate that the classical incidence of NPC likely occurs at the clinically predicted rate of ~1:90,000 and suggest that there may be a late-onset phenotype or variant form with an incidence potentially as high as 1:19,000-36,000. […] Leveraging existing whole-exome sequence data, we estimated the disease incidence of NPC using both bioinformatic tools and manual curation. With respect to classical NPC disease, we estimate that the incidence of NPC1 and NPC2 are on the order of 1/92,000 and 1/2,900,000, respectively, with a combined incidence of ~1/89,000. These estimates are in agreement with previous clinical estimates. Thus, our data do not support significant underascertainment of classical NPC cases.

• #24 Niemann-Pick disease type B | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/niemann-pick-disease-type-b-2?lang=us

  NPD-B is a pan-ethnic, unlike NPD-A which is much more common in Ashkenazi Jews. Its onset is usually in late childhood and is much less severe than NPD-A, with a good prognosis of survival into adulthood. […] The definitive diagnosis of those diseases (NPD-A and B) is based on the demonstration of residual acid sphingomyelinase activity in peripheral blood leukocytes to be 10 percent of controls. […] SMPD1 mutation can also be evaluated by genetic testing, but it has proven to be most effective in patients of Ashkenazi descent (for type A disease) and of North African descent (for type B disease).

• #25 International Niemann-Pick Disease Registry – International Niemann-Pick Disease Alliance (INPDA)

  https://www.inpda.org/inpdr/

  The International Niemann-Pick Disease Registry (INPDR) is a new concept in rare disease registries; it is a unifying force with the power to increase knowledge and understanding of Niemann-Pick diseases. […] The INPDR is now established as an independently governed rare disease registry for the global collection of Niemann-Pick data, encompassing both Acid Sphingomyelinase Deficiency (ASMD type A and B) and Niemann-Pick disease type C (NPC). […] The data held in the registry contributes to: Describing the epidemiology and natural history of ASMD Niemann-Pick disease and Niemann-Pick type C. […] However, it is our hope that the International Niemann-Pick Disease Registry (INPDR) will help increase knowledge and understanding of Niemann-Pick diseases through the facilitation of an improved and more supportive healthcare environment for patients affected by Niemann-Pick disease(s).

• #26 International Niemann-Pick Disease Registry – International Niemann-Pick Disease Alliance (INPDA)

  https://www.inpda.org/inpdr/

  The INPDR vision is the creation and ongoing development of a comprehensive, international data resource, specific to Niemann-Pick diseases which benefits patients by increasing understanding of these rare conditions, encouraging efficient and timely diagnosis, enabling progress in research and clinical trials, and facilitating the development of therapeutic interventions.

• #27 Niemann-Pick disease | Newborn Screening

  https://newbornscreening.hrsa.gov/conditions/niemann-pick-disease

  It is estimated that approximately 15 babies are born with this condition each year in the United States. […] Newborn screening for ASMD requires collecting a small amount of blood from your baby’s heel. […] Screening measures how much ASM enzyme is in your baby’s blood. This enzyme is responsible for breaking down sphingomyelin. Babies with a low level of this enzyme might have ASMD. […] If your baby’s blood spot screening result for ASMD is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans. […] You should complete any recommended follow-up testing as soon as possible. Babies and infants with this condition can have serious health problems if they are not diagnosed and treated quickly. […] False-positive newborn screening results for this condition can happen.

• #28 Advancing diagnosis and treatment of Niemann-Pick C disease through biomarker discovery

  https://www.explorationpub.com/Journals/ent/Article/100412

  TCG is also the only blood-based biomarker suitable for NPC newborn screening. […] A pilot screen based on quantification of TCG in dried blood spots is underway, the results of which should provide a more accurate assessment of the true disease incidence and facilitate therapeutic intervention in pre-symptomatic patients. […] Finally, the drug development landscape for NPC remains challenging. […] Thus, there is an urgent need for new biomarkers that could serve as surrogate endpoints to accelerate drug approval.

• #29 Niemann-Pick disease: Causes, symptoms, treatment, and more

  https://www.medicalnewstoday.com/articles/niemann-pick-disease

  Niemann-Pick disease is a rare genetic disorder that renders the body incapable of metabolizing cholesterol and other lipids inside of cells. […] The disease is extremely rare, with only 500 reported cases of NPC worldwide and 1,200 cases of types A and B (NPA and NPB). […] It is a life threatening disorder, particularly for younger people. […] The National Organization for Rare Disorders reports that 95% of people with NPC have a mutation in NPC1, which is located on chromosome 18. […] The diagnosis of Niemann-Pick disease centers around clinical observations and blood or skin cell biopsies. […] As it is so rare, most doctors see few if any cases of Niemann-Pick disease throughout their career. […] There is no known cure for Niemann-Pick disease and no way to prevent it because it is entirely hereditary. However, early diagnosis and proper treatment may improve life expectancy for some people with type B or C.

• #30 High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets | Genetics in Medicine

  https://www.nature.com/articles/gim201525

  Niemann-Pick disease type C (NPC) is a recessive, neurodegenerative, lysosomal storage disease caused by mutations in either NPC1 or NPC2. The diagnosis is difficult and frequently delayed. Ascertainment is likely incomplete because of both these factors and because the full phenotypic spectrum may not have been fully delineated. Given the recent development of a blood-based diagnostic test and the development of potential therapies, understanding the incidence of NPC and defining at-risk patient populations are important. […] Our data suggest an incidence rate for NPC1 and NPC2 of 1/92,104 and 1/2,858,998, respectively. Evaluation of common NPC1 variants, however, suggests that there may be a late-onset NPC1 phenotype with a markedly higher incidence, on the order of 1/19,000-1/36,000. […] We determined a combined incidence of classical NPC of 1/89,229, or 1.12 affected patients per 100,000 conceptions, but predict incomplete ascertainment of a late-onset phenotype of NPC1. This finding strongly supports the need for increased screening of potential patients.

• #31 High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets | Genetics in Medicine

  https://www.nature.com/articles/gim201525

  However, our data suggest that there may be significant underascertainment of a late-onset NPC1 phenotype. This late-onset phenotype may present as visceral-only or neurological mild NPC1 and have a potential incidence of 1/19,000-1/36,000. Further work is necessary to fully delineate this late-onset NPC1 phenotype, but this study suggests that NPC should be considered in individuals with visceral lipidosis or unexplained neurological and psychiatric symptoms.

• #32 Niemann-Pick disease, SMPD1-related | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/niemann-pick-disease-smpd1-related/

  How Common Is Niemann-Pick Disease, SMPD1-Related? The exact incidence of Niemann-Pick disease (including both NPD-A and NPD-B) is unknown but estimated to be 1 in 250,000 individuals. NPD-A is the most common form of Niemann-Pick disease, accounting for 85% of cases. NPD-A is more common in individuals of Ashkenazi Jewish descent, while NPD-B is most common in the Maghreb region of North Africa, which includes Algeria, Morocco, and Tunisia. […] There are currently no effective treatments for NPD-A. Medical professionals can attempt to treat the symptoms through physical therapy, monitoring of nutrition, and medication to help sleep disorders. However, treatment cannot stop the decline caused by the disease. […] There is no treatment to address the cause of NPD-B. However, individual symptoms such as high cholesterol can be addressed. Those with clotting problems may need blood transfusions, while those with breathing problems may need supplemental oxygen. Individuals with NPD-B should be monitored to ensure they are getting the proper nutrition for growth from their diet.

• #33 Niemann-Pick Disease Type C Market Insight, Epidemiology

  https://www.globenewswire.com/news-release/2024/05/06/2875577/28124/en/Niemann-Pick-Disease-Type-C-Market-Insight-Epidemiology-and-Market-Forecast-2032-Featuring-Zevra-Therapeutics-Azafaros-Cyclo-Therapeutics-and-IntraBio.html

  The report delivers an in-depth understanding of the Niemann-Pick Disease Type C, historical and forecasted epidemiology as well as the Niemann-Pick Disease Type C market trends in the United States, EU4, the United Kingdom and Japan. […] There were 787 diagnosed prevalent cases of Niemann-Pick Disease Type C (NPC) estimated to have occurred in the 7MM in 2022, of which 335 of the accounted cases were estimated to be from the US alone, and these cases are anticipated to increase during the forecast period. […] The diagnosed prevalent Niemann-Pick Disease Type C (NPC) cases were divided into Gender-specific cases. The Gender-specific diagnosed prevalent cases of Niemann-Pick Disease Type C (NPC) are categorized into Males and Females, with 354 and 433 cases, respectively, in the 7MM in 2022, which will increase by 2032.

• #34 Orphanet: Infantile neurovisceral acid sphingomyelinase deficiency

  https://www.orpha.net/en/disease/detail/77292

  The birth prevalence of acid sphingomyelinase deficiency (combined both Niemann-Pick disease (NPD) types A and B) is estimated between 1/167,000-250,000 in Europe. Niemann-Pick disease type A (NPD-A) is more prevalent in the Ashkenazi Jewish population, where the estimated birth rate is estimated at 1/33,000. […] NPD-A is inherited in an autosomal recessive manner. Genetic counseling should be offered to at-risk couples informing them that there is a 25% risk of having an affected child at each pregnancy.

• #35 Niemann-Pick disease type A – Metabolic Support UKAccessibility ToolsIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://metabolicsupportuk.org/condition/niemann-pick-disease-type-a/

  Currently, reports suggest that this condition affects 1 in 250,000 individuals. This condition is more common in the Ashkenazi Jewish populations, where it is estimated to effect 1 – 40,000 people. There is no current indication that this metabolic condition is more common in males than it is females. […] ASMD NP- A can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier. […] Once your child is diagnosed, you can speak to a genetic counsellor. They can explain how you may have inherited NPD. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own. If you have previously had a child with ASMD NP- A and go on to have further children, their New-born Screening test should be carried out within 24-48 hours of birth.

• #36 Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice | bioRxiv

  https://www.biorxiv.org/content/10.1101/2024.06.07.597901v1.full-text

  Niemann-Pick disease, type C (NPC) is a rare, fatal neurodegenerative disease with an incidence of ~1 in 100,000 live births. […] While small molecule therapeutics provide some amelioration, all fail to address the root cause of the disorder – the absence of the NPC1 protein that causes subsequent morbidity and mortality. Gene therapy can provide the replacement of the dysfunctional NPC1 protein to treat the disease. […] Given the irreversible nature of neurodegeneration and lethality, NPC individuals remain in dire need of effective treatments that a durable gene therapy might provide. […] We and others have previously demonstrated AAV9 vectors can effectively improve survival and delay NPC1 disease progression in a severe NPC1 murine model (Npc1m1N). […] Both direct CNS administration (intracerebroventricular or intracisternal magna) and systemic administration (retro-orbital or intracardiac) have successfully ameliorated disease in these mice.

• #37 Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice | bioRxiv

  https://www.biorxiv.org/content/10.1101/2024.06.07.597901v1.full-text

  While there is a robust foundation for gene therapy studies largely focused on neonatal intervention in severely affected Npc1m1N mice, further studies using variable times of delivery and mouse models that recapitulate attenuated forms of the disease have not been fully explored. […] Intervention prior to clinical onset of neurologic symptoms in NPC is currently challenging because newborn screening for NPC1 is not yet included on the Recommended Uniform Screening Panel (RUSP) and the average diagnostic delay remains ~4.1 years. […] More than 600 pathogenic or likely pathogenic NPC1 variants have been described, most of which are missense mutations. […] Here we build on our previous work, using systemic administration of an AAV9-elongation factor 1α (shortened)-hNPC1 vector to treat various mouse models of NPC1 at timepoints later in disease progression.

• #38 Optimization of systemic AAV9 gene therapy in Niemann-Pick disease type C1 mice | bioRxiv

  https://www.biorxiv.org/content/10.1101/2024.06.07.597901v1.full-text

  In aggregate, our results provide foundational preclinical data for the advancement of AAV9-EF1a(s)-hNPC1 as a disease modulating therapy for individuals with NPC1 deficiency. […] We examined dose, age at intervention, and type of genetic variation (null vs missense mutation) as key factors for optimization of systemically delivered AAV9-hNPC1. […] Importantly, several clinical trials using peripherally administered gene therapy for neurological diseases are well underway. […] In aggregate, our studies demonstrate that systemic delivery of AAV9-EF1a(s)-hNPC1 can have significant impact on NPC1 disease phenotype and improve survival in severe and milder mouse models of the disorder.

• #39 Niemann-Pick Disease Type C Signs & Symptoms | Rush | Rush System

  https://www.rush.edu/kids/conditions/niemann-pick-disease-type-c

  Niemann-Pick disease type C is estimated to affect about one in every 100,000 children. […] Through a clinical trial, Rush is the first center in the Midwest, and one of only eleven in the U.S., currently screening patients and offering VTS-270, a new drug being studied as a possible way to slow the progression of Niemann-Pick disease type C. […] Researchers at Rush are leading an effort to find life-changing treatment for this devastating disease. Through a clinical trial, Rush is currently screening patients and offering a drug called VTS-270, which is being developed by Vtesse, a Maryland-based biotech company that focuses on treatments for rare diseases. Early findings indicate that the treatment may slow the rate of progression of the disease.

• #40 Niemann-Pick Disease Type C Market Insight, Epidemiology

  https://www.globenewswire.com/news-release/2024/05/06/2875577/28124/en/Niemann-Pick-Disease-Type-C-Market-Insight-Epidemiology-and-Market-Forecast-2032-Featuring-Zevra-Therapeutics-Azafaros-Cyclo-Therapeutics-and-IntraBio.html

  The distribution of diagnosed prevalent cases of Niemann-Pick disease type C by type was categorized into early-infantile ( 2 years), late-infantile (2 to 6 years), juvenile (6 to 15 years), and adolescent/adult-onset (=15 years), with 100, 227, 235, and 226 cases in the 7MM in 2022. […] The total market size of Niemann-Pick Disease Type C (NPC) in the 7MM was approximately USD 34 million in 2022 and is projected to increase during the forecast period 2023-2032.

• #41 Niemann-Pick Disease Type C Market: Epidemiology, Industry Trends, Share, Size, Growth, Opportunity, and Forecast 2024-2034

  https://www.researchandmarkets.com/reports/5970326/niemann-pick-disease-type-c-market?srsltid=AfmBOopEU_G9rPOcHNwNgyq5cPVu393mYuXf9Q5vD7N4D1pqQZgM8jfg

  The 7 major Niemann-Pick disease type C markets are expected to exhibit a CAGR of 16.9% during 2023-2034. […] The report also provides the current and future patient pool across the seven major markets. According to the report the United States has the largest patient pool for Niemann-Pick disease type C and also represents the largest market for its treatment. […] Historical, current, and future epidemiology scenario […] What is the number of prevalent cases (2018-2034) of Niemann-Pick disease type C across the seven major markets? […] What is the size of the Niemann-Pick disease type C patient pool (2018-2023) across the seven major markets? […] What would be the forecasted patient pool (2024-2034) across the seven major markets? […] What are the key factors driving the epidemiological trend of Niemann-Pick disease type C? […] What will be the growth rate of patients across the seven major markets?

• #42 Niemann-Pick Disease Type A Market Size | Share 2034

  https://www.imarcgroup.com/niemann-pick-disease-type-a-market

  The 7 major Niemann-Pick disease type A markets are expected to exhibit a CAGR of 4.31% during 2024-2034. […] The escalating incidences of genetic mutations affecting the SMPD1 gene, which can lead to the harmful accumulation of sphingomyelin in various body organs, predominantly the liver, spleen, and brain, are primarily driving the Niemann-Pick disease type A market. […] IMARC Group’s new report provides an exhaustive analysis of the Niemann-Pick disease type A market in the United States, EU5 (Germany, Spain, Italy, France, and United Kingdom) and Japan. This includes treatment practices, in-market, and pipeline drugs, share of individual therapies, market performance across the seven major markets, market performance of key companies and their drugs, etc. […] According to the report the United States has the largest patient pool for Niemann-Pick disease type A and also represents the largest market for its treatment.

• #43 Niemann-Pick Disease Type A Market Size | Share 2034

  https://www.imarcgroup.com/niemann-pick-disease-type-a-market

  The report also provides the current and future patient pool across the seven major markets. […] What is the number of prevalent cases (2018-2034) of Niemann-Pick disease type A across the seven major markets? […] What is the size of the Niemann-Pick disease type A patient pool (2018-2023) across the seven major markets? […] What would be the forecasted patient pool (2024-2034) across the seven major markets? […] What are the key factors driving the epidemiological trend of Niemann-Pick disease type A? […] What will be the growth rate of patients across the seven major markets?

• #44 Niemann-Pick Disease Type C Market Insight, Epidemiology, and Market Forecast – 2034

  https://www.linkedin.com/pulse/niemann-pick-disease-type-c-market-insight-forecast-gaurav-bora-9oy4c

  Niemann-Pick Disease Type C is an autosomal recessive genetic disorder. The prevalence of Niemann-Pick Disease Type C varies globally, but it is estimated that 1 in 100,000 to 1 in 120,000 people worldwide are affected. […] Studies show that Niemann-Pick Disease Type C accounts for around 3% of all lysosomal storage disorders, making it a significant yet rare disorder. Given its complex nature and multi-organ involvement, diagnosing Niemann-Pick Disease Type C remains challenging, often leading to delays in treatment. However, advancements in genetic testing and biomarkers are improving early diagnosis rates, which is expected to help in managing the disease more effectively. […] Epidemiology and Treatment Insight: Offers detailed insights into the epidemiology and treatment of Niemann-Pick Disease Type C across the 7MM (United States, Europe, and Japan).

• #45

  https://step2.medbullets.com/pediatrics/120118/niemann-pick-disease

  Epidemiology […] Incidence […] rare, however […] in Niemann-Pick disease (NPD) type A, it is more common in the Ashkenazi Jewish population. […] […] […] Demographics […] 1:1 male-to-female ratio […] age bracket […] dependent on type of NPD […] type A can present as early as 3 months of age […] type B typically occurs in early childhood. […] […] […] Location […] neural tissue (NPD type A) and visceral organs such as […] the spleen and liver (NPD type A and B); as well as the lung and bone marrow (NPD type B).

• #46 Niemann–Pick Disease Type C | CheckRare

  https://checkrare.com/niemann-pick-disease-type-c/

  The incidence of NPC is very low affecting approximately 1 baby in every 100,000 live births. Patients with NPC are categorized by age of onset: (1) neonatal; (2) early infantile onset (2 years); (3) late infantile onset (2-6 years); (4) juvenile onset (6-15 years); or (5) adolescent/adult onset (15 years). […] According to a U.K. population analysis, patients with late-infantile onset and juvenile onset seem most common, with an average age at the time of diagnosis of 4.6 and 11.5 years, respectively. […] Disease prevalence does not seem to be higher in any specific region of the world; however, some epidemiologic evidence suggests that the Hispanic populations of southern New Mexico and Colorado seem to be at higher incidence. […] The only risk factor that seems confirmed by evidence is a familial history (specifically, in a parent or sibling) of NPC.

• #47

  https://www.omim.org/entry/607616

  McGovern et al. (2013) performed a systematic evaluation of morbidity and mortality in Niemann-Pick type B disease in a total of 103 patients (49 males, 54 females, age range 1-72 years) studied between 1992 and 2012. Serious morbidities included significant neurologic, hepatic, and cardiac disease. Thirteen patients had some degree of neurologic impairment. Nine had cirrhosis or liver failure requiring transplantation. Coronary artery and valvular heart disease were present in 9 patients. Of note, only 4 patients were oxygen-dependent, although progressive pulmonary disease is a well-described feature of Niemann-Pick disease. During the follow-up period 18 deaths occurred. Median age of death was 15.5 years (range 1-72). Causes of death included pneumonia, liver failure, and hemorrhage. The majority of deaths (12 of the 18) occurred in patients younger than 21 years, yielding a mortality rate of 19% in the pediatric population.

• #48 Niemann-Pick disease type C | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/niemann-pick-disease-type-c-2?lang=us

  NPD-C is inherited as an autosomal recessive disorder with an estimated minimal incidence of 1/120,000 live births 2. […] Although invariable NPD-C leads to premature death, in almost all cases before the age of 50 years of age, the rate of progression is highly variable. Age of onset of systemic features (e.g. hepatosplenomegaly) is not a good predictor, whereas the age at which neurological impairment becomes evident does correlate with survival: the earlier the onset of neurological signs and symptoms, the shorter the life expectancy 2.

• #49

  https://www.omim.org/entry/607616

  Cassiman et al. (2016) reviewed the cause of death in 85 patients with Niemann-Pick B and B variant. Of these, 27 were newly reported and 58 were abstracted from the literature. Common disease-related morbidities included splenomegaly (97%), hepatomegaly (91%), liver dysfunction (83%), and pulmonary disease (75%). Among those with symptom onset after 18 years of age, respiratory disease was the primary cause of death in 44%, with bleeding and cardiac disease each accounting for 22%. Among those with symptom onset before 18 years of age, respiratory disease and liver disease each accounted for 28% of deaths and neurodegenerative disease accounted for 15% of deaths. Among those with chronic visceral acid sphingomyelinase deficiency (ASMD), respiratory disease and liver disease accounted for 31% and 29% of deaths, respectively. Among those with chronic neurovisceral ASMD, respiratory and neurodegenerative disease each accounted for 23% of deaths and were followed by liver disease at 19%.

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