CACH syndrome
| Classification according to ICD-10 | |
|---|---|
| E75.2 | Other sphingolipidoses |
| ICD-10 online (WHO version 2019) | |
The CACH syndrome , English acronym for C hildhood A taxie with C entral nervous system H ypomyelinisation , is a very rare congenital leukoencephalopathy with the eponymous main features.
Synonyms are: infantile ataxia with diffuse hypomyelination of the CNS; Leukoencephalopathy with loss of white matter in the brain; Myelinosis centralis diffusa; Cree leukoencephalopathy; Ovarioleukodystrophie English leukoencephalopathy with vanishing white matter; Vanishing White Matter; VWM
The first description comes from 1997 by Marjo van der Knaap and colleagues.
distribution
The frequency is unknown, about 150 people have been reported to be affected. Inheritance is autosomal - recessive .
root cause
Depending on the underlying mutation , the following types can be distinguished:
- EIF2B1 , mutation in EIF2B1 - gene on chromosome 12 locus q24.31
- EIF2B2 , mutation in the EIF2B2 gene on chromosome 14 locus q24.3
- EIF2B3 , mutation in the EIF2B3 gene on chromosome 1 locus p34.1
- EIF2B4 , mutation in the EIF2B4 gene on chromosome 2 locus p23.3
- EIF2B5 , mutation in the EIF2B5 gene on chromosome 3 locus q27.1
The EIF2B genes code for subunits of the initiation factors for translation in eukaryotes that are involved in the regulation of protein synthesis under cellular stress.
Clinical manifestations
Clinical criteria are:
- The onset of the disease usually occurs in early childhood
- Spasticity , ataxia
- Worsening with attacks of fever
- Death after 5 to 10 years
The clinical picture is different. So there are severe cases in infants ( leukoencephalopathy Type Cree ), forms without neurological symptoms, lighter and later starting curves ( ovário leukodystrophy ), also called English eIF2B-related leukoencephalopathies referred.
diagnosis
In the magnetic resonance imaging a diffuse change can white matter with cyst formation are detected.
Histopathologically, there is an orthochromatic leukodystrophy with cavities and increased oligodendrocytes .
The mutation can be detected human genetically .
therapy
No causal treatment is known; corticosteroids may be helpful.
Prospect of healing
The prognosis seems to depend on the age of onset, with a more severe course if onset early.
literature
- SR Vaidya, SB Desai, SV Khadilkar, NA Mehta: Childhood ataxia with cerebral hypomyelination (CACH) syndrome: a study of three siblings. In: Neurology India. Volume 52, Number 3, September 2004, pp. 372-374, PMID 15472431 .
- D. Rodriguez, A. Gelot, B. della Gaspera, O. Robain, G. Ponsot, LL Sarliève, S. Ghandour, A. Pompidou, A. Dautigny, P. Aubourg, D. Pham-Dinh: Increased density of oligodendrocytes in childhood ataxia with diffuse central hypomyelination (CACH) syndrome: neuropathological and biochemical study of two cases. In: Acta neuropathologica. Volume 97, Number 5, May 1999, pp. 469-480, PMID 10334484 .
Individual evidence
- ↑ a b c d e f CACH syndrome. In: Orphanet (Rare Disease Database).
- ↑ MS van der Knaap, PG Barth, FJ Gabreëls, E. Franzoni, JH Begeer, H. Stroink, JJ Rotteveel, J. Valk: A new leukoencephalopathy with vanishing white matter. In: Neurology. Volume 48, Number 4, April 1997, pp. 845-855, PMID 9109866 .
- ↑ Leucoencephalopathy with vanishing white matter. In: Online Mendelian Inheritance in Man . (English)
- ↑ Leukoencephalopathy, progressive, with ovarian failure. In: Online Mendelian Inheritance in Man . (English)
