Details of Disease

General Information of Disease (ID: DISUUQJF)

• Disease Name: Fabry disease
• Synonyms: ceramide trihexosidase deficiency; Fabry disease, Cardiac variant; Gla deficiency; hereditary dystopic lipidosis; angiokeratoma, diffuse; Alpha-galactosidase A deficiency; angiokeratoma corporis diffusum; Fabry's disease; deficiency of melibiase; Fabry disease; alpha galactosidase deficiency; diffuse angiokeratoma; Fd; Anderson-Fabry disease
• Disease Class: 5C56: Lysosomal disease
• Definition: Fabry disease (FD) is a progressive, inherited, multisystemic lysosomal storage disease characterized by specific neurological, cutaneous, renal, cardiovascular, cochleo-vestibular and cerebrovascular manifestations.
• Disease Hierarchy:
  DISEC08E: Sphingolipidosis
  DISMFQKM: Developmental anomaly of metabolic origin
  DISUUQJF: Fabry disease
• ICD Code:
  ICD-11: ICD-11: 5C56.01
  ICD-9: ICD-9: 272.7
  Expand ICD-9: 272.7
• Disease Identifiers:
  MONDO ID: MONDO_0010526
  MESH ID: D000795
  UMLS CUI: C0002986
  OMIM ID: 301500
  MedGen ID: 8083
  HPO ID: HP:0001071
  Orphanet ID: 324
  SNOMED CT ID: 124464003

Drug-Interaction Atlas (DIA) of This Disease

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Agalsidase alfa	DMWM37T	Approved	NA	[1]
Agalsidase beta	DMU980N	Approved	NA	[1]
Migalastat	DMFIQ2H	Approved	Small molecular drug	[2]
Pegunigalsidase alfa	DMOUW65	Approved	NA	[3]

This Disease is Treated as An Indication in 6 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Lucerastat	DMI7JF3	Phase 3	NA	[4]
Venglustat	DMLPEZS	Phase 2	NA	[5]
4D-310	DMNG59Y	Phase 1/2	Gene therapy	[6]
AVR-RD-01	DMC1XHK	Phase 1/2	Gene therapy	[7]
isaralgagene civaparvovec	DM5SSPZ	Phase 1/2	Gene therapy	[8]
ST-920	DMOJIPG	Phase 1/2	Gene therapy	[8]

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
JR-051	DM64FRU	Investigative	NA	[9]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ARSB	TTESQTG	Limited	Biomarker	[10]
CTH	TTLQUZS	Limited	Biomarker	[11]
CTSF	TTJOKD1	Limited	Biomarker	[12]
DAAM2	TTN0Z6H	Limited	Altered Expression	[13]
G6PC	TTBQMJ8	Limited	Genetic Variation	[14]
MGAM	TTXWASR	Limited	Biomarker	[15]
CTSA	TT5NILS	Strong	Genetic Variation	[16]
GAL	TTXZAJ5	Strong	Biomarker	[17]
GLB1	TTNGJPH	Strong	Biomarker	[18]
LAMP2	TTULDG7	Strong	Biomarker	[19]
GAA	TTLPC70	Definitive	Biomarker	[20]
GLA	TTIS03D	Definitive	X-linked	[21]
IDS	TTNY2AP	Definitive	Biomarker	[22]
TTR	TTPOYU7	Definitive	Biomarker	[23]
UGCG	TTPHEX3	Definitive	Biomarker	[24]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
MANBA	DEMH6UB	Limited	Biomarker	[25]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACD	OTC54EPO	Limited	Genetic Variation	[26]
AGA	OTNWT1WB	Limited	Altered Expression	[27]
ATAD1	OTJ02XFL	Limited	Genetic Variation	[28]
MLC1	OTCNZLSP	Limited	Biomarker	[29]
MPEG1	OT7DAO0F	Limited	Biomarker	[30]
MYO5B	OTCKL3W3	Limited	Altered Expression	[13]
NAIP	OTLA925F	Limited	Altered Expression	[31]
NPHS2	OTLCNUII	Limited	Altered Expression	[32]
RPS27	OTFXKY7P	Limited	Biomarker	[30]
SCARB2	OTN929M8	Limited	Biomarker	[12]
SYNPO	OTICDJAB	Limited	Altered Expression	[33]
INF2	OT8ZM13C	Disputed	Biomarker	[34]
MCF2L	OTEURA8N	moderate	Biomarker	[35]
C16orf82	OT77Z5Y5	Strong	Biomarker	[36]
NAGA	OTNUEUZY	Strong	Biomarker	[37]
PRKAG2	OTHTAM54	Strong	Genetic Variation	[38]
TNNT1	OT8PBOAR	Strong	Biomarker	[36]
GLA	OTBSR6DT	Definitive	X-linked	[21]

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [2] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
• [3] FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 761161.
• [4] ClinicalTrials.gov (NCT03737214) A Study to Evaluate the Long-term Safety and Tolerability of Lucerastat in Adult Subjects With Fabry Disease. U.S. National Institutes of Health.
• [5] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800036945)
• [6] ClinicalTrials.gov (NCT04519749) An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease. U.S.National Institutes of Health.
• [7] ClinicalTrials.gov (NCT03454893) FAB- GT Open-Label, Study Of Efficacy and Safety Of AVR-RD-01 for Treatment -Naive Subjects With Classic Fabry Disease. U.S. National Institutes of Health.
• [8] ClinicalTrials.gov (NCT04046224) A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy, in Subjects With Fabry Disease (STAAR). U.S.National Institutes of Health.
• [9] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [10] Treatment of lysosomal storage disorders : progress with enzyme replacement therapy.Drugs. 2007;67(18):2697-716. doi: 10.2165/00003495-200767180-00005.
• [11] Measurement of urinary CDH and CTH by tandem mass spectrometry in patients hemizygous and heterozygous for Fabry disease.J Inherit Metab Dis. 2005;28(1):35-48. doi: 10.1007/s10545-005-5263-4.
• [12] A Human Stem Cell Model of Fabry Disease Implicates LIMP-2 Accumulation in Cardiomyocyte Pathology.Stem Cell Reports. 2019 Aug 13;13(2):380-393. doi: 10.1016/j.stemcr.2019.07.004. Epub 2019 Aug 1.
• [13] Unravelling the mechanism of action of enzyme replacement therapy in Fabry disease.J Hum Genet. 2016 Feb;61(2):143-9. doi: 10.1038/jhg.2015.123. Epub 2015 Oct 22.
• [14] Rapid molecular diagnosis of genetic diseases by high resolution melting analysis: fabry and glycogen storage 1A diseases.Genet Test Mol Biomarkers. 2014 Jan;18(1):3-7. doi: 10.1089/gtmb.2013.0371. Epub 2013 Dec 17.
• [15] Enzyme enhancers for the treatment of Fabry and Pompe disease.Mol Ther. 2015 Mar;23(3):456-64. doi: 10.1038/mt.2014.224. Epub 2014 Nov 20.
• [16] Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome.Int J Mol Sci. 2019 Sep 3;20(17):4298. doi: 10.3390/ijms20174298.
• [17] Plasma Globotriaosylsphingosine Level as a Primary Screening Target for Fabry Disease in Patients With Left Ventricular Hypertrophy.Circ J. 2019 Aug 23;83(9):1901-1907. doi: 10.1253/circj.CJ-19-0110. Epub 2019 Jul 12.
• [18] Tuning glycosidase inhibition through aglycone interactions: pharmacological chaperones for Fabry disease and GM1 gangliosidosis.Chem Commun (Camb). 2012 Jul 4;48(52):6514-6. doi: 10.1039/c2cc32065g. Epub 2012 May 23.
• [19] Lysosome-associated protein 1 (LAMP-1) and lysosome-associated protein 2 (LAMP-2) in a larger family carrier of Fabry disease.Gene. 2014 Feb 15;536(1):118-22. doi: 10.1016/j.gene.2013.11.063. Epub 2013 Dec 12.
• [20] Case study on the pathophysiology of Fabry disease: abnormalities of cellular membranes can be reversed by substrate reduction in vitro.Biosci Rep. 2017 Apr 28;37(2):BSR20160402. doi: 10.1042/BSR20160402. Print 2017 Apr 30.
• [21] 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.
• [22] Absence of -galactosidase cross-correction in Fabry heterozygote cultured skin fibroblasts.Mol Genet Metab. 2015 Feb;114(2):268-73. doi: 10.1016/j.ymgme.2014.11.005. Epub 2014 Nov 12.
• [23] Screening for Fabry disease and Hereditary ATTR amyloidosis in idiopathic small-fiber and mixed neuropathy.Muscle Nerve. 2019 Mar;59(3):354-357. doi: 10.1002/mus.26348. Epub 2018 Dec 4.
• [24] Lucerastat, an Iminosugar for Substrate Reduction Therapy: Tolerability, Pharmacodynamics, and Pharmacokinetics in Patients With Fabry Disease on Enzyme Replacement.Clin Pharmacol Ther. 2018 Apr;103(4):703-711. doi: 10.1002/cpt.790. Epub 2017 Aug 28.
• [25] Morphological and biochemical studies of human beta-mannosidosis: identification of a novel beta-mannosidase gene mutation.Br J Dermatol. 2003 Jul;149(1):23-9. doi: 10.1046/j.1365-2133.2003.05365.x.
• [26] Heterozygote detection in angiokeratoma corporis diffusum (Anderson-Fabry disease). Studies on plasma, leucocytes, and hair follicles.J Med Genet. 1977 Apr;14(2):91-9. doi: 10.1136/jmg.14.2.91.
• [27] Development of a model system for neuronal dysfunction in Fabry disease.Mol Genet Metab. 2016 Sep;119(1-2):144-50. doi: 10.1016/j.ymgme.2016.07.010. Epub 2016 Jul 22.
• [28] Fabry disease: six gene rearrangements and an exonic point mutation in the alpha-galactosidase gene.J Clin Invest. 1989 Apr;83(4):1390-9. doi: 10.1172/JCI114027.
• [29] Insight into hypertrophied hearts: a cardiovascular magnetic resonance study of papillary muscle mass and T1 mapping.Eur Heart J Cardiovasc Imaging. 2017 Sep 1;18(9):1034-1040. doi: 10.1093/ehjci/jew187.
• [30] Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy.J Inherit Metab Dis. 2018 Mar;41(2):209-219. doi: 10.1007/s10545-017-0098-3. Epub 2017 Nov 15.
• [31] Apoptotic abnormalities in differential gene expression in peripheral blood mononuclear cells from children with Fabry disease.Acta Paediatr. 2008 Apr;97(457):48-52. doi: 10.1111/j.1651-2227.2008.00654.x.
• [32] Tandem mass spectrometry analysis of urinary podocalyxin and podocin in the investigation of podocyturia in women with preeclampsia and Fabry disease patients.Clin Chim Acta. 2019 Aug;495:67-75. doi: 10.1016/j.cca.2019.03.1615. Epub 2019 Mar 19.
• [33] A heterozygous female with Fabry disease due to a novel -galactosidase A mutation exhibits a unique synaptopodin distribution in vacuolated podocytes.Clin Nephrol. 2015 May;83(5):301-8. doi: 10.5414/CN108317.
• [34] Unexpectedly high prevalence of rare genetic disorders in kidney transplant recipients with an unknown causal nephropathy.Clin Transplant. 2014 Sep;28(9):995-1003. doi: 10.1111/ctr.12408. Epub 2014 Jul 18.
• [35] Screening for Fabry disease in patients undergoing dialysis for chronic renal failure in Turkey: identification of new case with novel mutation.Gene. 2013 Sep 15;527(1):42-7. doi: 10.1016/j.gene.2013.05.050. Epub 2013 Jun 10.
• [36] Value of cardiac biomarker measurement in the differential diagnosis of infiltrative cardiomyopathy patients with preserved left ventricular systolic function.J Thorac Dis. 2018 Aug;10(8):4966-4975. doi: 10.21037/jtd.2018.07.56.
• [37] Use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease.Am J Hum Genet. 2009 Nov;85(5):569-80. doi: 10.1016/j.ajhg.2009.09.016. Epub 2009 Oct 22.
• [38] Glycogen storage diseases presenting as hypertrophic cardiomyopathy.N Engl J Med. 2005 Jan 27;352(4):362-72. doi: 10.1056/NEJMoa033349.