Details of Disease

General Information of Disease (ID: DIS6H1IB)

Disease Name	Krabbe disease
Synonyms	Krabbe leukodystrophy; GLD; galactosylceramide Beta-galactosidase deficiency; galactosylceramide lipidosis; beta galactocerebrosidase deficiency; diffuse globoid body sclerosis; GALC deficiency; galactocerebrosidase deficiency; Krabbe's leukodystrophy; globoid cell leukoencephalopathy; Leukodystrophy, Krabbe's; Krabbe disease; globoid cell leukodystrophy; Krabbe's disease; galactosylceramidase deficiency
Disease Class	8A44: Leukodystrophy
Definition	A lysosomal disorder that affects the white matter of the central and peripheral nervous systems. It includes infantile, late-infantile/juvenile and adult forms.\|Pathogenesis: rapid and nearly complete disappearance of myelin and myelin-forming cells--the oligodendrocytes in the central nervous system and the Schwann cells in the peripheral nervous system, reactive astroytic gliosis, and infiltration of the unique and often multinucleated macrophages ("globoid cells") that contain strongly periodic acid-Schiff (PAS)-positive materials. A normally insignificant but highly cytotoxic metabolite, galactosylsphingosine (psychosine), is also a substrate of galactosylceramidase and is considered to play a critical role in the pathogenesis[PMID:14572137]
Disease Hierarchy	DISSYRHC: Hereditary peripheral neuropathy DISVY1TT: Leukodystrophy DIS1L24B: Eye degenerative disorder DISEC08E: Sphingolipidosis DIS6H1IB: Krabbe disease
ICD Code	ICD-11 ICD-11: 8A44.4
Disease Identifiers	MONDO ID MONDO_0009499 MESH ID D007965 UMLS CUI C0023521 OMIM ID 245200 MedGen ID 44131 Orphanet ID 487 SNOMED CT ID 192782005

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
FBX-101	DMZR3OJ	Phase 1/2	Gene therapy	[1]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ARSA	TTYQANR	Strong	Biomarker	[2]
GLB1	TTNGJPH	Strong	Biomarker	[3]
SNCA	TT08OSU	Strong	Biomarker	[4]
GALC	TT5IZRB	Definitive	Autosomal recessive	[5]
GALC	TT5IZRB	Definitive	Genetic Variation	[6]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
GCLC	DESYL1F	moderate	Biomarker	[7]
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This Disease Is Related to 7 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DEGS1	OT4WXPKW	moderate	Biomarker	[8]
GCA	OTAJ7ZHG	moderate	Biomarker	[7]
GMCL1	OTRZHUFV	moderate	Biomarker	[7]
PIEZO1	OTBG1FU4	moderate	Genetic Variation	[9]
PSAP	OTUOEKY7	moderate	Genetic Variation	[6]
RNF139	OT0PR1X5	Strong	Biomarker	[10]
GALC	OT1F6BZK	Definitive	Autosomal recessive	[5]
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⏷ Show the Full List of 7 DOT(s)

References

1	ClinicalTrials.gov (NCT05739643) A Phase 1b Clinical Study of Intravenous AAVrh10 Vector Expressing GALC in Krabbe Subjects Who Previously Received Hematopoietic Stem Cell Transplantation (REKLAIM). U.S.National Institutes of Health.
2	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.
3	Sphingolipidoses in Turkey.Brain Dev. 2004 Sep;26(6):363-6. doi: 10.1016/j.braindev.2003.09.006.
4	Analysis of age-related changes in psychosine metabolism in the human brain.PLoS One. 2018 Feb 26;13(2):e0193438. doi: 10.1371/journal.pone.0193438. eCollection 2018.
5	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.
6	Rare Saposin A deficiency: Novel variant and psychosine analysis.Mol Genet Metab. 2020 Feb;129(2):161-164. doi: 10.1016/j.ymgme.2019.08.001. Epub 2019 Aug 5.
7	Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system.Toxicol Appl Pharmacol. 2017 Mar 1;318:69-78. doi: 10.1016/j.taap.2017.01.008. Epub 2017 Jan 20.
8	Gene therapy for metachromatic leukodystrophy.J Neurosci Res. 2016 Nov;94(11):1169-79. doi: 10.1002/jnr.23792.
9	Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis.Am J Med Genet A. 2018 Dec;176(12):2829-2834. doi: 10.1002/ajmg.a.40533. Epub 2018 Sep 23.
10	Immuno-lectin histochemistry and ultrastructure in two cases of globoid cell leukodystrophy (Krabbe's disease).Clin Neuropathol. 1992 Nov-Dec;11(6):312-7.