Details of Disease

General Information of Disease (ID: DISKS5FO)

• Disease Name: Niemann-pick disease
• Synonyms: type A Niemann-Pick disease; sphingomyelinase deficiency disease; sphingomyelin/cholesterol lipidosis; sphingomyelin lipidosis; lipoid histiocytosis (classical phosphatide); lipoid histiocytosis; Niemann-Pick disease, subacute juvenile form; Niemann-Pick disease with cholesterol esterification block
• Disease Class: 5C56: Lysosomal disease
• Definition: A group of inherited, severe metabolic disorders in which sphingomyelin accumulates in lysosomes in cells. The lysosomes normally transport material through and out of the cell.
• Disease Hierarchy:
  DIS6JEVM: Non-Langerhans cell histiocytosis
  DISEC08E: Sphingolipidosis
  DISKS5FO: Niemann-pick disease
• ICD Code:
  ICD-11: ICD-11: 5C56.0Y
  Expand ICD-11: '5C56.0Y
• Disease Identifiers:
  MONDO ID: MONDO_0001982
  MESH ID: D009542
  UMLS CUI: C0028064
  MedGen ID: 10348
  SNOMED CT ID: 58459009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 4 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
VTS-270	DMMQHPB	Phase 3	Small molecular drug	[1]
GZ402665	DMHHI1F	Phase 2/3	NA	[2]
Acid sphingomyelinase	DMDY5ZI	Phase 1	NA	[3]
RhASM enzyme replacement therapy (acid sphingomyelinase deficiency)	DM3VZL1	Phase 1	NA	[4]

This Disease is Treated as An Indication in 1 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Trappsol Cyclo	DMVNWP4	Investigative	Small molecular drug	[5]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
SMPD1	TTJTM88	moderate	Genetic Variation	[6]
CHIT1	TTDYX6T	Strong	Altered Expression	[7]
GBA	TT1B5PU	Strong	Biomarker	[8]
GALC	TT5IZRB	Definitive	Biomarker	[9]
SMPD1	TTJTM88	Definitive	Autosomal recessive	[10]
SMPD2	TTE5VI6	Definitive	Altered Expression	[11]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SMPDL3A	DEQJ8N3	Strong	Genetic Variation	[12]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
NPC1	OTRIPICX	Strong	Biomarker	[13]
NPC2	OTE9UEJC	Strong	Genetic Variation	[14]
NPB	OT0U82T3	Definitive	Biomarker	[15]
RPS27	OTFXKY7P	Definitive	Biomarker	[16]
SMPD1	OTZSMA54	Definitive	Autosomal recessive	[10]

References

• [1] ClinicalTrials.gov (NCT03643562) Niemann-Pick Type C Treatment With Adrabetadex for Symptoms of Brain and Nervous System. U.S. National Institutes of Health.
• [2] ClinicalTrials.gov (NCT02004691) Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of Genzyme.
• [4] ClinicalTrials.gov (NCT00410566) Safety Study of rhASM Enzyme Replacement Therapy in Adults With Acid Sphingomyelinase Deficiency (Niemann-Pick Disease). U.S. National Institutes of Health.
• [5] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [6] Niemann-Pick disease A or B in four pediatric patients and SMPD1 mutation carrier frequency in the Mexican population.Ann Hepatol. 2019 Jul-Aug;18(4):613-619. doi: 10.1016/j.aohep.2018.12.004. Epub 2019 May 12.
• [7] Allelic Frequency of a 24-bp Duplication in Exon 10 of the CHIT1 Gene in the General Iranian Population.Genet Test Mol Biomarkers. 2016 Jan;20(1):31-6. doi: 10.1089/gtmb.2015.0116. Epub 2015 Dec 1.
• [8] Lipids regulate the hydrolysis of membrane bound glucosylceramide by lysosomal -glucocerebrosidase.J Lipid Res. 2017 Mar;58(3):563-577. doi: 10.1194/jlr.M073510. Epub 2017 Jan 26.
• [9] Alpha galactosidase A activity in Parkinson's disease.Neurobiol Dis. 2018 Apr;112:85-90. doi: 10.1016/j.nbd.2018.01.012. Epub 2018 Feb 2.
• [10] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [11] Enzyme activities and phospholipid storage patterns in brain and spleen samples from Niemann-Pick disease variants: a comparison of neuropathic and non-neuropathic forms.J Inherit Metab Dis. 1986;9(1):59-71. doi: 10.1007/BF01813904.
• [12] The structure and catalytic mechanism of human sphingomyelin phosphodiesterase like 3a--an acid sphingomyelinase homologue with a novel nucleotide hydrolase activity. FEBS J. 2016 Mar;283(6):1107-23.
• [13] Characterization of the Filovirus-Resistant Cell Line SH-SY5Y Reveals Redundant Role of Cell Surface Entry Factors.Viruses. 2019 Mar 19;11(3):275. doi: 10.3390/v11030275.
• [14] Niemann-Pick diseases.Handb Clin Neurol. 2013;113:1717-21. doi: 10.1016/B978-0-444-59565-2.00041-1.
• [15] Niemann-Pick disease type A and B are clinically but also enzymatically heterogeneous: pitfall in the laboratory diagnosis of sphingomyelinase deficiency associated with the mutation Q292 K.Neuropediatrics. 2003 Dec;34(6):301-6. doi: 10.1055/s-2003-44668.
• [16] Newborn Screening for Lysosomal Storage Disorders in Illinois: The Initial 15-Month Experience.J Pediatr. 2017 Nov;190:130-135. doi: 10.1016/j.jpeds.2017.06.048. Epub 2017 Jul 17.