Details of Disease

General Information of Disease (ID: DISPXOTO)

• Disease Name: Stargardt disease
• Synonyms: juvenile onset macular degeneration; Stargardt macular dystrophy; Stargardt disease 1; Stargardt 1; fundus flavimaculatus
• Disease Class: 9B70: Inherited retinal dystrophy
• Definition: Stargardt disease, also known as Stargardt 1 (STGD1), is an autosomal recessive form of retinal dystrophy that is usually characterized by a progressive loss of central vision associated with irregular macular and perimacular yellow-white fundus flecks, and a so-called ''beaten bronze'' atrophic central macular lesion.
• Disease Hierarchy:
  DIST8UDW: Familial flecked retinopathy
  DIS0XS2C: Age-related macular degeneration
  DISPXOTO: Stargardt disease
• ICD Code:
  ICD-11: ICD-11: 9B70
  ICD-10: ICD-10: H35.5
• Disease Identifiers:
  MONDO ID: MONDO_0019353
  MESH ID: D000080362
  UMLS CUI: C0271093
  MedGen ID: 75734
  Orphanet ID: 827
  SNOMED CT ID: 47673003

Drug-Interaction Atlas (DIA) of This Disease

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Tinlarebant	DM6JYUO	Phase 3	Small molecule	[1]
ALK-001	DMDXZ6O	Phase 2	NA	[2]
hESC-derived RPE (MA09-hRPE)	DMUSTAW	Phase 1/2	NA	[3]
MA09-hRPE cells	DMDNBJ1	Phase 1/2	NA	[2]
SAR422459	DMM4A19	Phase 1/2	NA	[4]
StarGen Stargardt's disease gene therapy	DM7K2TG	Phase 1/2	NA	[4]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PROM1	TTXMZ81	Supportive	Autosomal dominant	[5]
PROM1	TTXMZ81	moderate	Genetic Variation	[6]
ABCG2	TTIMJ02	Strong	Biomarker	[7]
AMD1	TTBFROQ	Strong	Biomarker	[8]
CLN3	TTORF9W	Strong	Biomarker	[9]
CNGB3	TT0LJCG	Strong	Genetic Variation	[10]
FANCF	TTNZKFJ	Strong	Biomarker	[11]
GRM6	TTWRP2F	Strong	Genetic Variation	[12]
GUCY2D	TTWNFC2	Strong	Genetic Variation	[13]
PNPLA6	TTWAQU2	Strong	Genetic Variation	[14]
PPT1	TTSQC14	Strong	Biomarker	[15]
RPGR	TTHBDA9	Strong	Biomarker	[16]
TST	TT51OTS	Strong	Genetic Variation	[17]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCA4	DTM4YG0	Supportive	Autosomal dominant	[18]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CRB1	OTXYUNG0	Disputed	Genetic Variation	[19]
ABCA4	OTMA4IG9	Supportive	Autosomal dominant	[18]
ELOVL4	OT2M9W26	Supportive	Autosomal dominant	[18]
PROM1	OTBHV8NX	Supportive	Autosomal dominant	[5]
ITIH2	OTG3WBBE	moderate	Biomarker	[20]
PRPH2	OTNH2G5H	moderate	Genetic Variation	[21]
RDH8	OTSFFV9B	moderate	Biomarker	[22]
RPE	OT0XT3JU	moderate	Biomarker	[23]
CRX	OTH435SV	Strong	Genetic Variation	[13]
DPYS	OTLTUIVL	Strong	Genetic Variation	[24]
GNAZ	OTLTDTR8	Strong	Genetic Variation	[25]
NR2E3	OTO3GBHQ	Strong	Biomarker	[26]
NYX	OTAGXLYP	Strong	Biomarker	[12]
PCARE	OTUSRSB5	Strong	Genetic Variation	[27]
PDE6B	OTOJMB1V	Strong	Biomarker	[28]
PLXNA2	OTNNBJMQ	Strong	Biomarker	[29]
PRPH	OT6VUH78	Strong	Genetic Variation	[30]
SENP7	OTQJ05ZS	Strong	Genetic Variation	[31]

References

• [1] ClinicalTrials.gov (NCT05244304) Phase 3, Multicenter, Randomized, Double-Masked, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Tinlarebant in the Treatment of Stargardt Disease in Adolescent Subjects. U.S.National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] ClinicalTrials.gov (NCT01625559) Safety and Tolerability of MA09-hRPE Cells in Patients With Stargardt's Macular Dystrophy(SMD)
• [4] ClinicalTrials.gov (NCT01367444) Phase I/IIa Study of StarGen in Patients With Stargardt's Macular Degeneration. U.S. National Institutes of Health.
• [5] Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice. J Clin Invest. 2008 Aug;118(8):2908-16. doi: 10.1172/JCI35891.
• [6] PROM1 gene variations in Brazilian patients with macular dystrophy.Ophthalmic Genet. 2017 Jan-Feb;38(1):39-42. doi: 10.1080/13816810.2016.1275022. Epub 2017 Jan 17.
• [7] Binding of retinoids to ABCA4, the photoreceptor ABC transporter associated with Stargardt macular degeneration.Methods Mol Biol. 2010;652:163-76. doi: 10.1007/978-1-60327-325-1_9.
• [8] The dark atrophy with indocyanine green angiography in Stargardt disease.Invest Ophthalmol Vis Sci. 2012 Jun 26;53(7):3999-4004. doi: 10.1167/iovs.11-9258.
• [9] Timing of cognitive decline in CLN3 disease.J Inherit Metab Dis. 2018 Mar;41(2):257-261. doi: 10.1007/s10545-018-0143-x. Epub 2018 Feb 1.
• [10] Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases. Hum Mutat. 2005 Mar;25(3):248-58. doi: 10.1002/humu.20142.
• [11] ULTRAWIDEFIELD AUTOFLUORESENCE IN ABCA4 STARGARDT DISEASE.Retina. 2018 Feb;38(2):403-415. doi: 10.1097/IAE.0000000000001567.
• [12] Sorting out co-occurrence of rare monogenic retinopathies: Stargardt disease co-existing with congenital stationary night blindness.Ophthalmic Genet. 2014 Mar;35(1):51-6. doi: 10.3109/13816810.2013.865762. Epub 2014 Jan 7.
• [13] Cone rod dystrophies.Orphanet J Rare Dis. 2007 Feb 1;2:7. doi: 10.1186/1750-1172-2-7.
• [14] The clinical spectrum of inherited diseases involved in the synthesis and remodeling of complex lipids. A tentative overview.J Inherit Metab Dis. 2015 Jan;38(1):19-40. doi: 10.1007/s10545-014-9776-6. Epub 2014 Nov 21.
• [15] Stargardt's disease is not allelic to the genes for neuronal ceroid lipofuscinoses.J Med Genet. 1994 Mar;31(3):222-3. doi: 10.1136/jmg.31.3.222.
• [16] Reliability and Repeatability of Cone Density Measurements in Patients With Stargardt Disease and RPGR-Associated Retinopathy.Invest Ophthalmol Vis Sci. 2017 Jul 1;58(9):3608-3615. doi: 10.1167/iovs.17-21904.
• [17] Mutations in the peripherin/RDS gene are an important cause of multifocal pattern dystrophy simulating STGD1/fundus flavimaculatus. Br J Ophthalmol. 2007 Nov;91(11):1504-11. doi: 10.1136/bjo.2007.115659. Epub 2007 May 15.
• [18] Defective lipid transport and biosynthesis in recessive and dominant Stargardt macular degeneration. Prog Lipid Res. 2010 Oct;49(4):476-92. doi: 10.1016/j.plipres.2010.07.002. Epub 2010 Jul 13.
• [19] Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family.Eur J Hum Genet. 2013 Nov;21(11):1266-71. doi: 10.1038/ejhg.2013.23. Epub 2013 Feb 27.
• [20] Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.
• [21] The K153Del PRPH2 mutation differentially impacts photoreceptor structure and function.Hum Mol Genet. 2016 Aug 15;25(16):3500-3514. doi: 10.1093/hmg/ddw193. Epub 2016 Jun 29.
• [22] Acute Stress Responses Are Early Molecular Events of Retinal Degeneration in Abca4-/-Rdh8-/- Mice After Light Exposure.Invest Ophthalmol Vis Sci. 2016 Jun 1;57(7):3257-67. doi: 10.1167/iovs.15-18993.
• [23] Di-retinoid-pyridinium-ethanolamine (A2E) Accumulation and the Maintenance of the Visual Cycle Are Independent of Atg7-mediated Autophagy in the Retinal Pigmented Epithelium.J Biol Chem. 2015 Nov 27;290(48):29035-44. doi: 10.1074/jbc.M115.682310. Epub 2015 Oct 14.
• [24] Novel lipofuscin bisretinoids prominent in human retina and in a model of recessive Stargardt disease.J Biol Chem. 2009 Jul 24;284(30):20155-66. doi: 10.1074/jbc.M109.021345. Epub 2009 May 28.
• [25] Mapping of the human cone transducin alpha-subunit (GNAT2) gene to 1p13 and negative mutation analysis in patients with Stargardt disease.Genomics. 1995 Jan 1;25(1):288-90. doi: 10.1016/0888-7543(95)80139-d.
• [26] The Marshall M. Parks memorial lecture: making sense of early-onset childhood retinal dystrophies--the clinical phenotype of Leber congenital amaurosis.Br J Ophthalmol. 2010 Oct;94(10):1281-7. doi: 10.1136/bjo.2009.165654. Epub 2009 Oct 12.
• [27] Exome sequencing reveals novel and recurrent mutations with clinical significance in inherited retinal dystrophies.PLoS One. 2014 Dec 29;9(12):e116176. doi: 10.1371/journal.pone.0116176. eCollection 2014.
• [28] Assessment of tropism and effectiveness of new primate-derived hybrid recombinant AAV serotypes in the mouse and primate retina.PLoS One. 2013 Apr 9;8(4):e60361. doi: 10.1371/journal.pone.0060361. Print 2013.
• [29] Comparative analysis of autofluorescence and OCT angiography in Stargardt disease.Br J Ophthalmol. 2018 Sep;102(9):1204-1207. doi: 10.1136/bjophthalmol-2017-311000. Epub 2017 Oct 26.
• [30] Phenotypic variation including retinitis pigmentosa, pattern dystrophy, and fundus flavimaculatus in a single family with a deletion of codon 153 or 154 of the peripherin/RDS gene.Arch Ophthalmol. 1993 Nov;111(11):1531-42. doi: 10.1001/archopht.1993.01090110097033.
• [31] Color vision in Stargardt's disease.Int Ophthalmol. 1992 Nov;16(6):423-8. doi: 10.1007/BF00918432.