CARASAL

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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]

Contents

Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy
Other namesCARASAL
Autosomal dominant - en.svg
CARASAL is inherited in a autosomal dominant fashion.

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 inhertied 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]

Treatment

This disease doesn't have a cure, although symptomatic management is available. [1]

Prognosis

It is believed that life expectancy is similiar to unaffected person. [3]

History

CARASAL was described in 5 French patients by Herve et al. [14]

See also

References

  1. 1 2 Mancuso, M.; Arnold, M.; Bersano, A.; Burlina, A.; Chabriat, H.; Debette, S.; Enzinger, C.; Federico, A.; Filla, A.; Finsterer, J.; Hunt, D.; Lesnik Oberstein, S.; Tournier-Lasserve, E.; Markus, H. S. (2020). "Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology". European Journal of Neurology. 27 (6): 909–927. doi:10.1111/ene.14183. hdl: 1887/3184998 . ISSN   1468-1331.
  2. 1 2 3 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.; van der Knaap, Marjo S. (October 25, 2016). "Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL)". Neurology. 87 (17): 1777–1786. doi:10.1212/WNL.0000000000003251.
  3. 1 2 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)". Acta Neurologica Belgica. 119 (3): 299–303. doi:10.1007/s13760-019-01158-8. ISSN   2240-2993.
  4. ↑ "Orphanet: Cathepsin A-related arteriopathy-strokes-leukoencephalopathy". www.orpha.net. Retrieved February 14, 2025.
  5. 1 2 3 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.; van der Knaap, Marjo S. (October 25, 2016). "Cathepsin A–related arteriopathy with strokes and leukoencephalopathy (CARASAL)". Neurology. 87 (17): 1777–1786. doi:10.1212/WNL.0000000000003251.
  6. ↑ "CTSA cathepsin A [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved February 14, 2025.
  7. ↑ "autosomal dominant inheritance". www.cancer.gov. July 20, 2012. Retrieved February 14, 2025.
  8. ↑ Lynch, David S.; Rodrigues Brandão de Paiva, Anderson; Zhang, Wei Jia; Bugiardini, Enrico; Freua, Fernando; Tavares Lucato, Leandro; Macedo-Souza, Lucia Inês; Lakshmanan, Rahul; Kinsella, Justin A.; Merwick, Aine; Rossor, Alexander M.; Bajaj, Nin; Herron, Brian; McMonagle, Paul; Morrison, Patrick J. (May 1, 2017). "Clinical and genetic characterization of leukoencephalopathies in adults". Brain. 140 (5): 1204–1211. doi:10.1093/brain/awx045. ISSN   0006-8950. PMC   5405235 .
  9. ↑ 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 , retrieved February 14, 2025
  10. ↑ Canavero, I; Rifino, N; Montano, V; Pantoni, L; Gatti, L; Pollaci, G; Potenza, A; Carrozzini, T; Finsterer, J; Bersano, A (January 1, 2022). "Cognitive aspects of MELAS and CARASAL". Cerebral Circulation - Cognition and Behavior. 3: 100139. doi:10.1016/j.cccb.2022.100139. hdl: 2434/920557 . ISSN   2666-2450.
  11. ↑ 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". Neuron. 81 (3): 588–602. doi:10.1016/j.neuron.2013.11.015. ISSN   0896-6273. PMC   3935216 . Archived from the original on February 4, 2025.
  12. ↑ "Orphanet: Galactosialidosis". www.orpha.net. Retrieved February 14, 2025.
  13. ↑ Hwang, Yun Tae; Lakshmanan, Rahul; Davagnanam, Indran; Thompson, Andrew G.B.; Lynch, David S.; Houlden, Henry; Bajaj, Nin; Eriksson, Sofia H.; Bamiou, Doris-Eva; Warren, Jason D. (August 2017). "Brainstem phenotype of cathepsin A–related arteriopathy with strokes and leukoencephalopathy". Neurology Genetics. 3 (4). doi:10.1212/NXG.0000000000000165. ISSN   2376-7839. PMC   5499977 . Archived from the original on February 12, 2025.
  14. ↑ Hervé, Dominique; Chabriat, Hugues; Rigal, Mélanie; Dalloz, Marie-Amelie; Kawkabani Marchini, Aida; De Lepeleire, Jean; Fontaine, Bertrand; Ceuterick-de Groote, Chantal; Alili, Nassira; Mine, Manuele; Delaforge, Audrey; Bousser, Marie-Germaine; Guichard, Jean-Pierre; Martin, Jean-Jacques; Gray, Françoise (December 4, 2012). "A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome 20q13". Neurology. 79 (23): 2283–2287. doi:10.1212/WNL.0b013e3182768954.
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