Medicine:CARASAL
Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy (CARASAL) is a rare genetic disorder that is caused by mutation in a gene CTSA which is located on a chromosome 20.[1] This disease is allelic to Galactosialidosis.[2] This disease usually begins with a headache, decreased concentration, abnormalities in gait, lack of inhibition, also it usually presents with migraine, depression, vertigo and high blood preasure.[3]
| Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy | |
|---|---|
| Other names | CARASAL |
 | |
| CARASAL is inherited in an autosomal dominant fashion. | |
| Symptoms | Migraine, mini-stroke, facial palsy, dementia, depression, concentration problems, movement problems, vertigo, difficulty swallowing, slurred speech, sicca symptoms, problems with REM sleep, drug-resistant hypertension |
| Usual onset | 20s-40s |
| Causes | Genetic mutation |
| Diagnostic method | MRI, genetic testing |
| Prognosis | Normal life expectancy |
Symptoms
The signs of this disease are: migraine, mini-stroke, facial palsy, dementia, depression, problems with concentration and movements, vertigo, difficulty in swallowing, slurring of speech, sicca symptoms, problems with REM sleep and drug-resistant hypertension.[4]
This condition usually manifest in the third to fifth decades of life.[5]
Cause
CARASAL is caused by mutation of the CTSA which codes enzyme Cathespin A.[5] CTSA gene is located on 20q13.12.[6]
This disease is inherited in autosomal dominant fashion, which means that mutation of one gene copy is enough to cause the disorder.[7][5]
According to some studies, the c.973C→T (p.R325C) mutation is associated with that disorder.[8][2]
Pathophysiology
Cathespin A is a lysosomal enzyme which main function is to form complex between β-galactosidase and Neurominidase 1 in lysosomes to protect them from degradation.[9] Also it is known that Cathespin A degrades Endothelin-1 and consequently it is known that Endothelin-1 might cause inhibition of oligodendrocyte progenitor cell maturation and remyelination through reactive astrocytes mechanism.[10][11]
As mentioned at the beginning of the article, CARASAL is allelic to Galactosialidosis, although Galactosialidosis is an autosomal recessive disorder.[2][12]
Diagnosis
CARASAL can be diagnosed by MRI investigation and by confirmation of the mutation in CTSA gene, also CARASAL should be considered in case of: [13]
- Middle-age patients with Cerebral Small Vessel Disease (cSVD).
- Positive family history of stroke.
- Broad, unexplained, infra/supratentorial white and grey matter hyperintensities (a.k.a. bright signals on MRI image).
- Neurotological problems.
Treatment
This disease doesn't have a cure, although symptomatic management is available.[1]
Prognosis
It is believed that life expectancy is similar to unaffected person.[3]
History
CARASAL was described in 5 French patients by Herve et al.[14]
See also
- CADASIL (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts And Leukoencephalopathy)
- CARASIL (Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)
References
- ↑ 1.0 1.1 Mancuso, M.; Arnold, M.; Bersano, A.; Burlina, A.; Chabriat, H.; Debette, S.; Enzinger, C.; Federico, A. et al. (2020). "Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology" (in en). European Journal of Neurology 27 (6): 909–927. doi:10.1111/ene.14183. ISSN 1468-1331. PMID 32196841. https://onlinelibrary.wiley.com/doi/10.1111/ene.14183.
- ↑ 2.0 2.1 2.2 Bugiani, Marianna; Kevelam, Sietske H.; Bakels, Hannah S.; Waisfisz, Quinten; Ceuterick-de Groote, Chantal; Niessen, Hans W.M.; Abbink, Truus E.M.; Lesnik Oberstein, Saskia A.M.J. et al. (October 25, 2016). "Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL)". Neurology 87 (17): 1777–1786. doi:10.1212/WNL.0000000000003251. PMID 27664989. https://www.neurology.org/doi/10.1212/WNL.0000000000003251?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.
- ↑ 3.0 3.1 Finsterer, Josef; Scorza, Carla A.; Scorza, Fulvio A.; Wakil, Salma M. (September 1, 2019). "Update on hereditary, autosomal dominant cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL)" (in en). Acta Neurologica Belgica 119 (3): 299–303. doi:10.1007/s13760-019-01158-8. ISSN 2240-2993. PMID 31177426. https://link.springer.com/article/10.1007/s13760-019-01158-8.
- ↑ "Orphanet: Cathepsin A-related arteriopathy-strokes-leukoencephalopathy". https://www.orpha.net/en/disease/detail/575553.
- ↑ 5.0 5.1 5.2 Bugiani, Marianna; Kevelam, Sietske H.; Bakels, Hannah S.; Waisfisz, Quinten; Ceuterick-de Groote, Chantal; Niessen, Hans W.M.; Abbink, Truus E.M.; Lesnik Oberstein, Saskia A.M.J. et al. (October 25, 2016). "Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL)". Neurology 87 (17): 1777–1786. doi:10.1212/WNL.0000000000003251. PMID 27664989. https://www.neurology.org/doi/10.1212/WNL.0000000000003251.
- ↑ "CTSA cathepsin A [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/5476.
- ↑ "autosomal dominant inheritance" (in en). July 20, 2012. https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/autosomal-dominant-inheritance.
- ↑ Lynch, David S.; Rodrigues Brandão de Paiva, Anderson; Zhang, Wei Jia; Bugiardini, Enrico; Freua, Fernando; Tavares Lucato, Leandro; Macedo-Souza, Lucia Inês; Lakshmanan, Rahul et al. (May 1, 2017). "Clinical and genetic characterization of leukoencephalopathies in adults". Brain 140 (5): 1204–1211. doi:10.1093/brain/awx045. ISSN 0006-8950. PMID 28334938. PMC 5405235. https://academic.oup.com/brain/article/140/5/1204/3060041?login=false.
- ↑ Bose, Samuel J.; Ayagama, Thamali; Burton, Rebecca A. B. (January 1, 2022), Zelanis, André, ed., "Chapter 3 - Lysosomal proteases and their role in signaling pathways", Proteolytic Signaling in Health and Disease (Academic Press): pp. 41–61, ISBN 978-0-323-85696-6, https://www.sciencedirect.com/science/article/abs/pii/B978032385696600007X, retrieved February 14, 2025
- ↑ Canavero, I; Rifino, N; Montano, V; Pantoni, L; Gatti, L; Pollaci, G; Potenza, A; Carrozzini, T et al. (January 1, 2022). "Cognitive aspects of MELAS and CARASAL". Cerebral Circulation - Cognition and Behavior 3. doi:10.1016/j.cccb.2022.100139. ISSN 2666-2450. PMID 36324419. PMC 9616374. https://www.sciencedirect.com/science/article/pii/S2666245022001040.
- ↑ Hammond, Timothy R.; Gadea, Ana; Dupree, Jeff; Kerninon, Christophe; Nait-Oumesmar, Brahim; Aguirre, Adan; Gallo, Vittorio (February 2014). "Astrocyte-Derived Endothelin-1 Inhibits Remyelination through Notch Activation" (in en). Neuron 81 (3): 588–602. doi:10.1016/j.neuron.2013.11.015. ISSN 0896-6273. PMID 24507193.
- ↑ "Orphanet: Galactosialidosis". https://www.orpha.net/en/disease/detail/351.
- ↑ Hwang, Yun Tae; Lakshmanan, Rahul; Davagnanam, Indran; Thompson, Andrew G.B.; Lynch, David S.; Houlden, Henry; Bajaj, Nin; Eriksson, Sofia H. et al. (August 2017). "Brainstem phenotype of cathepsin A–related arteriopathy with strokes and leukoencephalopathy" (in en). Neurology Genetics 3 (4). doi:10.1212/NXG.0000000000000165. ISSN 2376-7839. PMID 28702507.
- ↑ Hervé, Dominique; Chabriat, Hugues; Rigal, Mélanie; Dalloz, Marie-Amelie; Kawkabani Marchini, Aida; De Lepeleire, Jean; Fontaine, Bertrand; Ceuterick-de Groote, Chantal et al. (December 4, 2012). "A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome 20q13". Neurology 79 (23): 2283–2287. doi:10.1212/WNL.0b013e3182768954. PMID 23175731. https://www.neurology.org/doi/10.1212/WNL.0b013e3182768954?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.
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