Details of Disease

General Information of Disease (ID: DIS3J8NN)

• Disease Name: Leukoencephalopathy with vanishing white matter
• Synonyms: vanishing White matter leukodystrophy with ovarian failure; leukoencephalopathy with vanishing WHITE matter; VWM; vanishing White matter leukodystrophy; CACH/VWM syndrome; CACH syndrome; vanishing white matter disease; vanishing white matter leukodystrophy; childhood ataxia with central nervous system hypomyelinization; childhood ataxia with central nervous system hypomyelination/vanishing white matter; ovarioleukodystrophy; CACH/VWM; Cree leukoencephalopathy; myelinosis centralis diffusa; leukoencephalopathy with vanishing white matter; CACH; childhood ataxia with central nervous system hypomyelination; childhood ataxia with diffuse central nervous system hypomyelination
• Definition: A new leukoencephalopathy, the CACH syndrome (Childhood Ataxia with Central nervous system Hypomyelination) or VWM (Vanishing White Matter) was identified on clinical and MRI criteria. Classically, this disease is characterized by (1) an onset between 2 and 5 years of age, with a cerebello-spastic syndrome exacerbated by episodes of fever or head trauma leading to death after 5 to 10 years of disease evolution, (2) a diffuse involvement of the white matter on cerebral MRI with a CSF-like signal intensity (cavitation), (3) a recessive autosomal mode of inheritance, (4) neuropathologic findings consistent with a cavitating orthochromatic leukodystrophy with increased number of oligodendrocytes with sometimes "foamy'' aspect.
• Disease Hierarchy:
  DISVY1TT: Leukodystrophy
  DIS3J8NN: Leukoencephalopathy with vanishing white matter
• Disease Identifiers:
  MONDO ID: MONDO_0800448
  MESH ID: D056784
  UMLS CUI: C1858991
  MedGen ID: 347037
  Orphanet ID: 135
  SNOMED CT ID: 447351004

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
TNFRSF12A	TTKPS7V	Limited	Biomarker	[1]
CSF1R	TT7MRDV	Strong	Biomarker	[2]
DPYD	TTZPS91	Strong	Biomarker	[3]
MTR	TTUTO39	Strong	Biomarker	[4]
RHOA	TTP2U16	Strong	Biomarker	[5]
SPP1	TT8ME6I	Strong	Biomarker	[6]

This Disease Is Related to 15 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
COL4A1	OTL6D1YE	Limited	Biomarker	[7]
TRIM21	OTA4UJCF	Limited	Altered Expression	[8]
ACOT12	OTN4RQK8	Strong	Biomarker	[9]
CHST11	OTNJJ5Q1	Strong	Biomarker	[10]
EIF2B3	OTG6HE7D	Strong	Biomarker	[11]
EIF2B5	OTV3R4RB	Strong	Biomarker	[12]
EIF2S1	OTM0GDTP	Strong	Posttranslational Modification	[13]
EIF2S3	OTARRES9	Strong	Posttranslational Modification	[13]
IFNK	OTO2WDPX	Strong	Biomarker	[14]
MSH5	OTDARQT3	Strong	Biomarker	[15]
RPP21	OT53MDNE	Strong	Biomarker	[15]
RTRAF	OTJ6NVMW	Strong	Biomarker	[12]
TCN2	OT41D0L3	Strong	Biomarker	[4]
TRIM39	OTESLVP9	Strong	Biomarker	[15]
SCP2	OTPAFCPQ	Definitive	Biomarker	[16]

References

• [1] The deposition of anti-DNA IgG contributes to the development of cutaneous lupus erythematosus.Immunol Lett. 2017 Nov;191:1-9. doi: 10.1016/j.imlet.2017.09.003. Epub 2017 Sep 9.
• [2] Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet. 2011 Dec 25;44(2):200-5. doi: 10.1038/ng.1027.
• [3] 5-FU multifocal inflammatory leukoencephalopathy and dihydropyrimidine dehydrogenase deficiency.Neurology. 2001 Jan 9;56(1):110-2. doi: 10.1212/wnl.56.1.110.
• [4] MTX-induced white matter changes are associated with polymorphisms of methionine metabolism. Neurology. 2005 Mar 8;64(5):912-3. doi: 10.1212/01.WNL.0000152840.26156.74.
• [5] Postzygotic inactivating mutations of RHOA cause a mosaic neuroectodermal syndrome.Nat Genet. 2019 Oct;51(10):1438-1441. doi: 10.1038/s41588-019-0498-4. Epub 2019 Sep 30.
• [6] [A case of FK 506-induced leukoencephalopathy].No To Shinkei. 2002 Jan;54(1):51-5.
• [7] Ophthalmological features associated with COL4A1 mutations.Arch Ophthalmol. 2010 Apr;128(4):483-9. doi: 10.1001/archophthalmol.2010.42.
• [8] TWEAK/Fn14 Activation Participates in Ro52-Mediated Photosensitization in Cutaneous Lupus Erythematosus.Front Immunol. 2017 May 31;8:651. doi: 10.3389/fimmu.2017.00651. eCollection 2017.
• [9] Evaluation of the endoplasmic reticulum-stress response in eIF2B-mutated lymphocytes and lymphoblasts from CACH/VWM patients.BMC Neurol. 2010 Oct 19;10:94. doi: 10.1186/1471-2377-10-94.
• [10] Identification and molecular analysis of glycosaminoglycans in cutaneous lupus erythematosus and dermatomyositis.J Histochem Cytochem. 2011 Mar;59(3):336-45. doi: 10.1369/0022155410398000. Epub 2011 Jan 12.
• [11] Postmortem Whole Exome Sequencing Identifies Novel EIF2B3 Mutation With Prenatal Phenotype in 2 Siblings.J Child Neurol. 2017 Sep;32(10):867-870. doi: 10.1177/0883073817712588. Epub 2017 Jun 9.
• [12] Analysis of a new begomovirus unveils a composite element conserved in the CP gene promoters of several Geminiviridae genera: Clues to comprehend the complex regulation of late genes.PLoS One. 2019 Jan 23;14(1):e0210485. doi: 10.1371/journal.pone.0210485. eCollection 2019.
• [13] Bergmann glia translocation: a new disease marker for vanishing white matter identifies therapeutic effects of Guanabenz treatment.Neuropathol Appl Neurobiol. 2018 Jun;44(4):391-403. doi: 10.1111/nan.12411. Epub 2017 Aug 1.
• [14] Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa.Ann Rheum Dis. 2018 Nov;77(11):1653-1664. doi: 10.1136/annrheumdis-2018-213197. Epub 2018 Jul 18.
• [15] Genome-wide association study identifies new susceptibility loci for cutaneous lupus erythematosus.Exp Dermatol. 2015 Jul;24(7):510-5. doi: 10.1111/exd.12708. Epub 2015 May 4.
• [16] Mutations in the gene encoding peroxisomal sterol carrier protein X (SCPx) cause leukencephalopathy with dystonia and motor neuropathy. Am J Hum Genet. 2006 Jun;78(6):1046-52. doi: 10.1086/503921. Epub 2006 Mar 29.