Niemann–Pick Disease Type E (historical): Comprehensive Disease Characteristics Report

Executive summary (current understanding)

Niemann–Pick disease “type E” (NPDE) is best understood as a historical, ill-defined nosologic label applied to rare, mostly adult presentations of Niemann–Pick–like storage disease. Modern expert sources emphasize that the molecular era split Niemann–Pick disorders into acid sphingomyelinase deficiency (ASMD; SMPD1; historically types A/B) and Niemann–Pick disease type C (NPC; NPC1/NPC2; historically type C and type D), and that “The nosology of types D and E NPD are no longer used.” (schuchman2017typesaand pages 1-3). A 2016 case report still used “type E” for an adult with Niemann–Pick cells and normal leukocyte acid sphingomyelinase and concluded that “the biochemical nature of type E still awaits clarification.” (zheng2016casereportrenal pages 3-5). Accordingly, a knowledge-base entry for “NP type E” should explicitly record that it is an obsolete label and that modern diagnosis should re-classify cases into ASMD, NPC, or another lysosomal disorder using enzyme activity, biomarkers, and molecular testing. (schuchman2017typesaand pages 1-3, geberhiwot2023consensusclinicalmanagement pages 11-13, geberhiwot2023consensusclinicalmanagement pages 13-14)

Key concepts and definitions (with modern reclassification)

What is the disease?

Historically, “Niemann–Pick disease” referred to patients with lipid storage and foam cells and overlapping clinical features such as hepatosplenomegaly, pulmonary insufficiency, and/or CNS involvement. (schuchman2017typesaand pages 1-3)

Modern work established two main metabolic etiologies: - ASMD (historical NPD types A and B): due to deficient acid sphingomyelinase (ASM) activity caused by SMPD1 mutations. (schuchman2017typesaand pages 1-3) - NPC (historical NPD type C; type D now included): due to defective intracellular cholesterol transport caused by NPC1 or NPC2 defects. (schuchman2017typesaand pages 1-3, patinoescobar2019niemannpickdiseasean pages 1-2)

“Type E” was historically used for some intermediate or adult cases, but authoritative review states it is no longer used (schuchman2017typesaand pages 1-3), and later case literature highlights it remains biochemically unclear (zheng2016casereportrenal pages 3-5).

Key identifiers (requested)

Evidence retrieved here did not provide an authoritative MONDO/MeSH/ICD/Orphanet identifier specifically for “Niemann–Pick disease type E.” Because “type E” is obsolete, modern resources typically index patients under ASMD or NPC rather than NPDE. (schuchman2017typesaand pages 1-3, geberhiwot2023consensusclinicalmanagement pages 4-5)

Ontology suggestion (to implement in KB, with uncertainty): treat “Niemann–Pick disease type E” as a historical synonym / deprecated term and map to parent concept “Niemann–Pick disease” with recommended reclassification to ASMD or NPC based on testing.

Synonyms / alternative names

• “Niemann–Pick disease type E” (historical) (zheng2016casereportrenal pages 3-5, schuchman2017typesaand pages 1-3)
• Many “type E” adult cases are described alongside sea-blue histiocytes/foamy macrophages in older literature; in modern practice such pathology may occur in ASMD and other lysosomal disorders and is not diagnostic alone. (geberhiwot2023consensusclinicalmanagement pages 9-11)

Evidence source type

The “type E” concept in the retrieved evidence is derived primarily from individual case reports / historical classification rather than aggregated, molecularly curated disease resources. (zheng2016casereportrenal pages 3-5, schuchman2017typesaand pages 1-3)

Etiology

Disease causal factors

NP type E (legacy): - A 2016 case report describes NP type E as rare and states that “the biochemical nature of type E still awaits clarification.” (zheng2016casereportrenal pages 3-5) - In that case, leukocyte ASM activity was normal, suggesting it did not fit classic ASMD A/B. (zheng2016casereportrenal pages 1-3)

Modern molecular entities that “type E” cases may represent: - ASMD: caused by pathogenic variants in SMPD1; diagnosis requires demonstrating deficient ASM activity and confirming genotype for counseling. (geberhiwot2023consensusclinicalmanagement pages 4-5, geberhiwot2023consensusclinicalmanagement pages 9-11, geberhiwot2023consensusclinicalmanagement pages 13-14) - NPC: caused by NPC1 or NPC2 mutations; NPC1 accounts for ~95% of families in a major review. (patinoescobar2019niemannpickdiseasean pages 1-2)

Risk factors / protective factors / gene–environment interaction

No NPDE-specific genetic or environmental risk/protective factors were identified in the retrieved evidence; NPDE is too ill-defined and rare for robust epidemiology. (zheng2016casereportrenal pages 3-5, schuchman2017typesaand pages 1-3)

Phenotypes

NP type E phenotype (what is known)

From a 2016 adult case report/literature framing: - NP type E described as an uncommon adult form, “possibly non-neuronopathic,” with “preserved mental status,” “variable hepatosplenomegaly,” and longer survival in historical descriptions. (zheng2016casereportrenal pages 1-3) - Renal involvement is described as rare but present in the reported case: kidney biopsy showed lipid storage/foam cells and EM showed lipid deposits in endothelial cells and podocytes, with proteinuria and renal insufficiency. (zheng2016casereportrenal pages 1-3) - Bone marrow Niemann–Pick cells supported diagnosis. (zheng2016casereportrenal pages 1-3, zheng2016casereportrenal pages 3-5)

Phenotype ontology suggestions (HPO; based on reported signs in retrieved evidence): - Splenomegaly (HP:0001744) - Hepatomegaly (HP:0002240) - Foam cells / lipid-laden macrophages (often captured under storage disease histopathology terms) - Proteinuria (HP:0000093) - Renal insufficiency (HP:0000083) - Ascites (HP:0001541)

Frequency estimates for NPDE are not available from the retrieved evidence (single case report + narrative). (zheng2016casereportrenal pages 1-3)

Phenotypes in modern entities (for reclassification)

Because NPDE is obsolete, phenotype expectations should follow the reclassified entity: - NPC registry data (INPDR, 2022) report common neurologic manifestations: cognitive impairment 78.5%, dysarthria 75.9%, ataxia 75.9%, VSGP 70.9%, dysphagia 69.6%; and splenomegaly recorded in 80% of adult-onset patients. (bolton2022clinicaldiseasecharacteristics pages 6-8) - ASMD guideline notes common manifestations include hepatosplenomegaly, interstitial lung disease, cytopenias, and dyslipidemia with low HDL and elevated cholesterol/triglycerides. (geberhiwot2023consensusclinicalmanagement pages 9-11)

Genetic / molecular information

Causal genes (modern mapping)

• ASMD: SMPD1 (acid sphingomyelinase). ASMD is explicitly synonymous with Niemann–Pick disease types A, B and A/B. (geberhiwot2023consensusclinicalmanagement pages 1-2)
• NPC: NPC1 or NPC2 mutations; NPC1 ~95% of families in a major review. (patinoescobar2019niemannpickdiseasean pages 1-2)

Pathogenic variants (recent, concrete examples)

ASMD (2024 Polish cohort): seven SMPD1 variants were identified; missense variants comprised 71% of alleles. (lipinski2024chronicacidsphingomyelinase pages 1-2)

NPC (INPDR 2022): p.I1061T variant was common (reported frequency in extracted registry summary). (bolton2022clinicaldiseasecharacteristics pages 6-8)

Modifier genes / epigenetics / chromosomal abnormalities No NPDE-specific modifier genes or epigenetic/chromosomal drivers were identified in the retrieved evidence.

Environmental information

No NPDE-specific environmental or lifestyle contributors were identified in the retrieved evidence.

Mechanism / pathophysiology

NP type E (legacy)

Mechanism is not established; the 2016 report explicitly indicates uncertainty and lack of a defined biochemical defect for type E. (zheng2016casereportrenal pages 3-5)

ASMD (SMPD1 / ASM deficiency)

ASMD is a lysosomal storage disease with sphingomyelin accumulation in tissues; ASMD pathology includes foam cell infiltration and multisystem involvement. (schuchman2017typesaand pages 1-3, geberhiwot2023consensusclinicalmanagement pages 9-11)

Diagnostic biomarker/pathophysiology linkage: - Lyso-sphingomyelin (lyso-SM) is described as the “most specific biomarker for ASMD” and is elevated in ASMD (lyso-SM509/PPCS may also be elevated but is seen in NPC too), supporting both diagnosis and monitoring. (geberhiwot2023consensusclinicalmanagement pages 11-13)

NPC (NPC1/NPC2 cholesterol trafficking defect)

NPC is described as a “cellular cholesterol trafficking defect,” with filipin staining of fibroblasts demonstrating lysosomal unesterified cholesterol accumulation. (patinoescobar2019niemannpickdiseasean pages 1-2)

GO term suggestions (mechanisms): - Lysosomal lipid catabolic process; cholesterol transport; endosome-to-lysosome transport; autophagy-related processes.

Cell type suggestions (CL): - Macrophage (foam cell); hepatocyte; alveolar macrophage; neurons (for neuronopathic forms).

Anatomical structures affected

NP type E (case-based)

• Reticuloendothelial tissues (bone marrow, liver, spleen) and kidney were involved in the 2016 case report, with lipid-laden cells and EM lipid deposits in renal structures. (zheng2016casereportrenal pages 1-3)

UBERON suggestions: spleen, liver, kidney, bone marrow.

ASMD/NPC (modern)

• ASMD frequently affects spleen/liver/lung and can involve multiple organ systems. (geberhiwot2023consensusclinicalmanagement pages 9-11)
• NPC is neurovisceral, with systemic signs often preceding neurologic involvement. (patinoescobar2019niemannpickdiseasean pages 1-2)

Temporal development

NP type E

Adult-onset is emphasized in type E descriptions; progression details and staging are not standardized due to rarity and obsolete classification. (zheng2016casereportrenal pages 1-3)

NPC (context)

INPDR (2022) includes adult-onset forms (20.8% adult neurological onset) and shows neurologic manifestations common across onset strata. (bolton2022clinicaldiseasecharacteristics pages 6-8)

ASMD (context)

ASMD spectrum includes chronic visceral adult presentations and a continuum of severity. (geberhiwot2023consensusclinicalmanagement pages 1-2)

Inheritance and population

NP type E

Inheritance is not well characterized for the legacy label. The 2016 report frames Niemann–Pick disease in general as autosomal recessive but indicates type E mechanism is unclear. (zheng2016casereportrenal pages 1-3, zheng2016casereportrenal pages 3-5)

Modern entities (for KB reclassification)

• ASMD: autosomal recessive due to SMPD1 mutations. (geberhiwot2023consensusclinicalmanagement pages 1-2)
• NPC: autosomal recessive due to NPC1 or NPC2 mutations. (patinoescobar2019niemannpickdiseasean pages 1-2)

Robust NPDE prevalence/incidence statistics were not identified.

Diagnostics

Key point: avoid “type E” as final diagnosis

Because “type E” is obsolete, modern diagnosis should proceed by distinguishing ASMD versus NPC (and other lysosomal disorders) with enzyme assay/biomarkers/genetics. (schuchman2017typesaand pages 1-3, geberhiwot2023consensusclinicalmanagement pages 11-13, geberhiwot2023consensusclinicalmanagement pages 13-14)

ASMD diagnostic workflow (2023 consensus)

• Perform ASM enzyme assay when ASMD suspected; diagnosis established by markedly reduced ASM activity in leukocytes or fibroblasts; DBS is increasingly used but should be confirmed due to false negatives/pre-analytical limitations. (geberhiwot2023consensusclinicalmanagement pages 9-11)
• SMPD1 sequencing is recommended to confirm diagnosis and enable counseling; VUS require functional evidence of enzyme deficiency. (geberhiwot2023consensusclinicalmanagement pages 11-13, geberhiwot2023consensusclinicalmanagement pages 13-14)
• Biomarkers: lyso-SM is most specific; multiplex MS/MS panels measuring lyso-SM, PPCS, lyso-Gb1 help differential diagnosis among ASMD, Gaucher, and NPC. (geberhiwot2023consensusclinicalmanagement pages 11-13)

NPC diagnostic workflow (2010 review)

• Primary lab diagnosis uses living skin fibroblasts to demonstrate lysosomal cholesterol accumulation after filipin staining; genotyping is useful to confirm especially in variant biochemical phenotypes. (patinoescobar2019niemannpickdiseasean pages 1-2)

“Type E” diagnostic clues in the 2016 case report

• Bone marrow Niemann–Pick cells, normal leukocyte ASM activity (distinguishing from types A/B), and elevated chitotriosidase were used in the case report to label NP type E. (zheng2016casereportrenal pages 1-3)

Outcome / prognosis

No NPDE-specific survival estimates were identified in the retrieved evidence. The 2016 report suggests longer survival than infantile forms in historical descriptions, but does not quantify survival. (zheng2016casereportrenal pages 1-3)

Treatment

NP type E (legacy)

The 2016 case report states no effective disease-specific therapy and describes supportive/symptomatic management. (zheng2016casereportrenal pages 1-3)

Modern disease-modifying therapies (relevant after reclassification)

ASMD: - 2023 ASMD guideline describes olipudase alfa (human recombinant ASM) as the first/only disease-modifying therapy and indicates it for long-term treatment of non-CNS manifestations, with approvals in multiple regions. (geberhiwot2023consensusclinicalmanagement pages 17-19) - A 2023 case report notes FDA approval in 2022 for olipudase alfa to treat non-CNS manifestations of ASM deficiency (NPD A/B/A-B) and reports biomarker confirmation via markedly elevated lyso-SM509 and low ASM activity. (sanchezvargas2023personalizedprecisionmedicine pages 3-4) - 2024 Polish cohort notes EMA approval (Dec 2020) and local availability timeline (Poland April 2024). (lipinski2024chronicacidsphingomyelinase pages 1-2)

NPC: - INPDR 2022 reported miglustat use in 62.4% of patients (85/203), mean duration just over 4 years. (bolton2022clinicaldiseasecharacteristics pages 6-8)

MAXO suggestions: - Enzyme replacement therapy; genetic counseling; supportive care; lipid/metabolic monitoring; pulmonary supportive management.

Prevention

No NPDE-specific prevention strategies were identified. For ASMD/NPC, prevention is primarily genetic counseling and family-based carrier/prenatal testing enabled by molecular confirmation. (geberhiwot2023consensusclinicalmanagement pages 13-14)

Other species / natural disease

Direct NPDE natural disease in other species was not identified. NPC has described feline/canine models with similar neurologic phenotypes (tremor/ataxia). (hovakimyan2013olfactorydeficitsin pages 1-2)

Model organisms (research applications)

ASMD (Niemann–Pick A/B) models

• ASM knockout (ASMKO; Smpd1) mice recapitulate biochemical deficiency, systemic foam cells, motor impairment (ataxia/tremor), progressive neurodegeneration, and shortened lifespan (~6–8 months). (sarna2001patternedcerebellarpurkinje pages 1-2)
• Purkinje cell degeneration is patterned and progressive; studies describe zebrin II–negative Purkinje cells lost earlier, with later involvement of other zones. (sarna2001patternedcerebellarpurkinje pages 2-4)
• ASMKO models also show inflammatory disease contributing to pulmonary and neurologic phenotypes and disruption of ceramide-mediated signaling. (schuchman2017typesaand pages 6-8)

NPC models

• Npc1−/− mouse models show neurodegeneration, hepatosplenomegaly, weight loss and early death (about 10 weeks in one description), and lysosomal accumulation of unesterified cholesterol and gangliosides. (hovakimyan2013olfactorydeficitsin pages 1-2)
• Therapeutic testing example: allopregnanolone treatment in NPC mice delayed demyelination and increased survival. (ahmad2005allopregnanolonetreatmentboth pages 1-2)

Recent developments and real-world implementations (prioritizing 2023–2024)

Modern NPDE-relevant “developments” largely concern ASMD and NPC, because NPDE is obsolete.

• Clinical management standardization (2023): A 2023 Orphanet Journal consensus guideline provides diagnostic and management statements for ASMD, including modern MS/MS enzyme assays, lyso-SM biomarkers, and SMPD1 sequencing for confirmation and counseling. (geberhiwot2023consensusclinicalmanagement pages 9-11, geberhiwot2023consensusclinicalmanagement pages 11-13, geberhiwot2023consensusclinicalmanagement pages 13-14)
• Real-world care burden (2023): US claims analysis (IQVIA Open Claims) quantified high multi-system healthcare use for ASMD type B with frequent liver/spleen/lung involvement and substantial hospitalization burden. (pulikottiljacob2023healthcareserviceuse pages 1-2, pulikottiljacob2023healthcareserviceuse pages 11-13)
• Biomarker-forward pediatric practice (2024): Polish pediatric ASMD follow-up highlights dried blood spot lyso-SM elevation, universal low HDL and low vitamin D, and 71% missense-allele burden in SMPD1 among 7 followed patients. (lipinski2024chronicacidsphingomyelinase pages 1-2, lipinski2024chronicacidsphingomyelinase pages 4-6)

Expert opinions / authoritative analysis

• Nosology: Schuchman & Desnick (2017) explicitly conclude: “The nosology of types D and E NPD are no longer used.” (schuchman2017typesaand pages 1-3)
• Guideline framing: 2023 consensus guidelines adopt ASMD terminology to distinguish SMPD1-related disease from NPC and provide evidence-graded statements on diagnosis and management. (geberhiwot2023consensusclinicalmanagement pages 4-5, geberhiwot2023consensusclinicalmanagement pages 9-11)

Relevant statistics and data (recent)

A summary of the most directly usable 2022–2024 quantitative data is provided in Artifact 02. (bolton2022clinicaldiseasecharacteristics pages 6-8, pulikottiljacob2023healthcareserviceuse pages 1-2, lipinski2024chronicacidsphingomyelinase pages 4-6)

Table: This table summarizes how historical Niemann-Pick subtype labels map to current molecularly defined entities. It is especially useful for clarifying why the legacy 'type E' designation is now considered obsolete and how modern diagnosis distinguishes ASMD from NPC.

Table: This table contrasts the historical, ambiguous Niemann-Pick “type E” label with current molecularly defined entities: ASMD and NPC. It is useful for showing why NP type E should be treated as an obsolete descriptor and how modern diagnostics distinguish overlapping adult presentations.

Table: This table compiles key 2022-2024 quantitative findings from NPC and ASMD studies that contextualize the obsolete Niemann-Pick disease type E label. It highlights how modern evidence is organized around molecularly defined disorders rather than historical subtype E.

Practical knowledge-base recommendation (implementation note)

For a Mendelian KB entry labeled “Niemann–Pick disease type E,” the evidence supports encoding it as a deprecated/historical diagnosis label with a strong directive to reclassify into ASMD vs NPC using enzyme assays, biomarkers (lyso-SM), and molecular testing (SMPD1; NPC1/NPC2). (schuchman2017typesaand pages 1-3, geberhiwot2023consensusclinicalmanagement pages 11-13, geberhiwot2023consensusclinicalmanagement pages 13-14)

References

1. (schuchman2017typesaand pages 1-3): Edward H. Schuchman and Robert J. Desnick. Types a and b niemann-pick disease. Molecular genetics and metabolism, 120 1-2:27-33, Jan 2017. URL: https://doi.org/10.1016/j.ymgme.2016.12.008, doi:10.1016/j.ymgme.2016.12.008. This article has 412 citations and is from a peer-reviewed journal.

2. (zheng2016casereportrenal pages 3-5): Z Zheng, C Cheng, W Zhao, Q Feng, C Li, and T Lou. Case report renal failure and ascites in a patient with niemann-pick disease: case report and literature review. Unknown journal, 2016.

3. (geberhiwot2023consensusclinicalmanagement pages 11-13): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.

4. (geberhiwot2023consensusclinicalmanagement pages 13-14): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.

5. (patinoescobar2019niemannpickdiseasean pages 1-2): Bonell Patiño-Escobar, Maria H Solano, Laura Zarabanda, Claudia P Casas, and Carlos Castro. Niemann-pick disease: an approach for diagnosis in adulthood. Cureus, May 2019. URL: https://doi.org/10.7759/cureus.4767, doi:10.7759/cureus.4767. This article has 15 citations.

6. (geberhiwot2023consensusclinicalmanagement pages 4-5): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.

7. (geberhiwot2023consensusclinicalmanagement pages 9-11): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.

8. (zheng2016casereportrenal pages 1-3): Z Zheng, C Cheng, W Zhao, Q Feng, C Li, and T Lou. Case report renal failure and ascites in a patient with niemann-pick disease: case report and literature review. Unknown journal, 2016.

9. (bolton2022clinicaldiseasecharacteristics pages 6-8): Shaun C. Bolton, Vina Soran, Mercedes Pineda Marfa, Jackie Imrie, Paul Gissen, Helena Jahnova, Reena Sharma, Simon Jones, Saikat Santra, Ellen Crushell, Miriam Stampfer, Maria Jose Coll, Charlotte Dawson, Toni Mathieson, James Green, Andrea Dardis, Bruno Bembi, Marc C. Patterson, Marie T. Vanier, and Tarekegn Geberhiwot. Clinical disease characteristics of patients with niemann-pick disease type c: findings from the international niemann-pick disease registry (inpdr). Orphanet Journal of Rare Diseases, Feb 2022. URL: https://doi.org/10.1186/s13023-022-02200-4, doi:10.1186/s13023-022-02200-4. This article has 52 citations and is from a peer-reviewed journal.

10. (geberhiwot2023consensusclinicalmanagement pages 1-2): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.

11. (lipinski2024chronicacidsphingomyelinase pages 1-2): Patryk Lipiński, Agnieszka Ługowska, and Anna Tylki-Szymańska. Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in polish patients: 2024 update. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 33:1163-1168, Oct 2024. URL: https://doi.org/10.17219/acem/193696, doi:10.17219/acem/193696. This article has 1 citations.

12. (geberhiwot2023consensusclinicalmanagement pages 17-19): Tarekegn Geberhiwot, Melissa Wasserstein, Subadra Wanninayake, Shaun Christopher Bolton, Andrea Dardis, Anna Lehman, Olivier Lidove, Charlotte Dawson, Roberto Giugliani, Jackie Imrie, Justin Hopkin, James Green, Daniel de Vicente Corbeira, Shyam Madathil, Eugen Mengel, Fatih Ezgü, Magali Pettazzoni, Barbara Sjouke, Carla Hollak, Marie T. Vanier, Margaret McGovern, and Edward Schuchman. Consensus clinical management guidelines for acid sphingomyelinase deficiency (niemann–pick disease types a, b and a/b). Orphanet Journal of Rare Diseases, Apr 2023. URL: https://doi.org/10.1186/s13023-023-02686-6, doi:10.1186/s13023-023-02686-6. This article has 105 citations and is from a peer-reviewed journal.

13. (sanchezvargas2023personalizedprecisionmedicine pages 3-4): JM Sanchez-Vargas and LJ Moreno-Giraldo. Personalized precision medicine of strategic health action in niemann-pick type a/b disease: case report. Journal of Clinical Images and Medical Case Reports, Apr 2023. URL: https://doi.org/10.52768/2766-7820/2363, doi:10.52768/2766-7820/2363. This article has 0 citations.

14. (hovakimyan2013olfactorydeficitsin pages 1-2): Marina Hovakimyan, Anja Meyer, Jan Lukas, Jiankai Luo, Volker Gudziol, Thomas Hummel, Arndt Rolfs, Andreas Wree, and Martin Witt. Olfactory deficits in niemann-pick type c1 (npc1) disease. PLoS ONE, 8:e82216, Dec 2013. URL: https://doi.org/10.1371/journal.pone.0082216, doi:10.1371/journal.pone.0082216. This article has 47 citations and is from a peer-reviewed journal.

15. (sarna2001patternedcerebellarpurkinje pages 1-2): Justyna Sarna, Silvia R. P. Miranda, Edward H. Schuchman, and Richard Hawkes. Patterned cerebellar purkinje cell death in a transgenic mouse model of niemann pick type a/b disease. European Journal of Neuroscience, 13:1873-1880, May 2001. URL: https://doi.org/10.1046/j.0953-816x.2001.01564.x, doi:10.1046/j.0953-816x.2001.01564.x. This article has 103 citations and is from a domain leading peer-reviewed journal.

16. (sarna2001patternedcerebellarpurkinje pages 2-4): Justyna Sarna, Silvia R. P. Miranda, Edward H. Schuchman, and Richard Hawkes. Patterned cerebellar purkinje cell death in a transgenic mouse model of niemann pick type a/b disease. European Journal of Neuroscience, 13:1873-1880, May 2001. URL: https://doi.org/10.1046/j.0953-816x.2001.01564.x, doi:10.1046/j.0953-816x.2001.01564.x. This article has 103 citations and is from a domain leading peer-reviewed journal.

17. (schuchman2017typesaand pages 6-8): Edward H. Schuchman and Robert J. Desnick. Types a and b niemann-pick disease. Molecular genetics and metabolism, 120 1-2:27-33, Jan 2017. URL: https://doi.org/10.1016/j.ymgme.2016.12.008, doi:10.1016/j.ymgme.2016.12.008. This article has 412 citations and is from a peer-reviewed journal.

18. (ahmad2005allopregnanolonetreatmentboth pages 1-2): Iram Ahmad, Silvia Lope‐Piedrafita, Xiaoning Bi, Chad Hicks, Yueqin Yao, Clara Yu, Elizabeth Chaitkin, Christine M. Howison, Lyndon Weberg, Theodore P. Trouard, and Robert P. Erickson. Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of niemann‐pick c mice. Journal of Neuroscience Research, 82:811-821, Dec 2005. URL: https://doi.org/10.1002/jnr.20685, doi:10.1002/jnr.20685. This article has 100 citations and is from a peer-reviewed journal.

19. (pulikottiljacob2023healthcareserviceuse pages 1-2): Ruth Pulikottil-Jacob, Michael L. Ganz, Marie Fournier, and Natalia Petruski-Ivleva. Healthcare service use patterns among patients with acid sphingomyelinase deficiency type b: a retrospective us claims analysis. Advances in Therapy, 40:2234-2248, Mar 2023. URL: https://doi.org/10.1007/s12325-023-02453-w, doi:10.1007/s12325-023-02453-w. This article has 8 citations and is from a peer-reviewed journal.

20. (pulikottiljacob2023healthcareserviceuse pages 11-13): Ruth Pulikottil-Jacob, Michael L. Ganz, Marie Fournier, and Natalia Petruski-Ivleva. Healthcare service use patterns among patients with acid sphingomyelinase deficiency type b: a retrospective us claims analysis. Advances in Therapy, 40:2234-2248, Mar 2023. URL: https://doi.org/10.1007/s12325-023-02453-w, doi:10.1007/s12325-023-02453-w. This article has 8 citations and is from a peer-reviewed journal.

21. (lipinski2024chronicacidsphingomyelinase pages 4-6): Patryk Lipiński, Agnieszka Ługowska, and Anna Tylki-Szymańska. Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in polish patients: 2024 update. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 33:1163-1168, Oct 2024. URL: https://doi.org/10.17219/acem/193696, doi:10.17219/acem/193696. This article has 1 citations.

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23. (lipinski2024chronicacidsphingomyelinase pages 3-4): Patryk Lipiński, Agnieszka Ługowska, and Anna Tylki-Szymańska. Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in polish patients: 2024 update. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 33:1163-1168, Oct 2024. URL: https://doi.org/10.17219/acem/193696, doi:10.17219/acem/193696. This article has 1 citations.

24. (lipinski2024chronicacidsphingomyelinase pages 2-3): Patryk Lipiński, Agnieszka Ługowska, and Anna Tylki-Szymańska. Chronic acid sphingomyelinase deficiency diagnosed in infancy/childhood in polish patients: 2024 update. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 33:1163-1168, Oct 2024. URL: https://doi.org/10.17219/acem/193696, doi:10.17219/acem/193696. This article has 1 citations.

Artifacts

• Edison artifact artifact-00
• Edison artifact artifact-01
• Edison artifact artifact-02