Details of Disease

General Information of Disease (ID: DIS3OMWS)

Disease Name	Metachromatic leukodystrophy
Synonyms	Scholz cerebral sclerosis; deficiency of cerebroside-sulfatase; MLD; arylsulfatase A deficiency; sulfatide lipoidosis
Disease Class	5C56: Lysosomal disease
Definition	A rare lysosomal storage disorder characterized by intralysosomal accumulation of sulfatides in various tissues, leading to progressive deterioration of motor and neurocognitive function.
Disease Hierarchy	DISSYRHC: Hereditary peripheral neuropathy DISVY1TT: Leukodystrophy DISEC08E: Sphingolipidosis DISFWL8F: Hereditary dementia DIS3OMWS: Metachromatic leukodystrophy
ICD Code	ICD-11 ICD-11: 5C56.02 Expand ICD-11 '5C56.02
Disease Identifiers	MONDO ID MONDO_0018868 MESH ID D007966 UMLS CUI C0023522 OMIM ID 250100 MedGen ID 6071 Orphanet ID 512 SNOMED CT ID 396338004

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
OTL-200	DMQNI7O	Approved	Gene therapy	[1]
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This Disease is Treated as An Indication in 4 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Drug 2696274	DMOEO0F	Phase 2	NA	[2]
GSK2696274	DMH3H3A	Phase 2	NA	[3]
HGT-1111	DMDZE3B	Phase 2	NA	[4]
SHP611	DMJ93C5	Phase 2	Recombinant protein	[5]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ARSB	TTESQTG	moderate	CausalMutation	[6]
GALC	TT5IZRB	moderate	Biomarker	[7]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ARSA	DEJ6FSR	Definitive	Autosomal recessive	[8]
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This Disease Is Related to 8 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DEGS1	OT4WXPKW	moderate	Biomarker	[9]
ELK4	OTVSSEOE	moderate	Biomarker	[10]
HOXB4	OTH1HRW5	moderate	Altered Expression	[11]
PSMA7	OTPHI6ST	moderate	Genetic Variation	[12]
PTPRH	OTDUHQGF	moderate	Biomarker	[10]
SCLT1	OT2ZSSP4	moderate	Biomarker	[10]
PSAP	OTUOEKY7	Strong	Genetic Variation	[13]
ARSA	OT1CU8VR	Definitive	Autosomal recessive	[8]
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⏷ Show the Full List of 8 DOT(s)

References

1	Clinical pipeline report, company report or official report of Orchard Therapeutics.
2	Clinical pipeline report, company report or official report of GlaxoSmithKline.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	ClinicalTrials.gov (NCT00681811) Open-Label Extension Study of Recombinant Human Arylsulfatase A (HGT-1111) in Late Infantile MLD. U.S. National Institutes of Health.
5	ClinicalTrials.gov (NCT03771898) A Study of Intrathecal SHP611 in Participants With Late Infantile Metachromatic Leukodystrophy (Embolden). U.S. National Institutes of Health.
6	Mucopolysaccharidosis type VI phenotypes-genotypes and antibody response to galsulfase.Orphanet J Rare Dis. 2013 Apr 4;8:51. doi: 10.1186/1750-1172-8-51.
7	Pervasive supply of therapeutic lysosomal enzymes in the CNS of normal and Krabbe-affected non-human primates by intracerebral lentiviral gene therapy.EMBO Mol Med. 2016 May 2;8(5):489-510. doi: 10.15252/emmm.201505850. Print 2016 May.
8	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.
9	Gene therapy for metachromatic leukodystrophy.J Neurosci Res. 2016 Nov;94(11):1169-79. doi: 10.1002/jnr.23792.
10	The mechanism for a 33-nucleotide insertion in mRNA causing sphingolipid activator protein (SAP-1)-deficient metachromatic leukodystrophy.Hum Genet. 1991 Jun;87(2):211-5. doi: 10.1007/BF00204185.
11	Successful treatment of metachromatic leukodystrophy using bone marrow transplantation of HoxB4 overexpressing cells.Mol Ther. 2010 Jul;18(7):1373-8. doi: 10.1038/mt.2010.74. Epub 2010 Apr 27.
12	Bone marrow harvesting from paediatric patients undergoing haematopoietic stem cell gene therapy.Bone Marrow Transplant. 2019 Dec;54(12):1995-2003. doi: 10.1038/s41409-019-0573-6. Epub 2019 May 31.
13	Late Infantile Metachromatic Leukodystrophy Due to Novel Pathogenic Variants in the PSAP Gene.J Mol Neurosci. 2019 Apr;67(4):559-563. doi: 10.1007/s12031-019-1259-7. Epub 2019 Jan 11.