What is Batten Disease?
Batten Disease is a general name used to describe inherited neuronal ceroid lipofuscinosis (NCL) diseases. The fatal neurodegenerative disorder caused by a mutation in the CLN3 gene has a juvenile onset, with symptoms beginning from four to six years old [1]. Batten Disease is estimated to impact roughly 2 to 4 out of 100,000 children in the United States, however, many more individuals may be carriers of a defect within the responsible gene [2]. There are 14 known variants of this disease, and because the underlying mechanisms of these diseases are still unknown, Batten Disease remains incurable.
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CLN3
CLN3 is a gene located on chromosome 16, and codes for a CLN3 transmembrane protein found in the plasma membrane of lysosomes in neuronal cells. Exons 7 and 8 are removed in Batten Disease patients with a juvenile onset [1]. The exact molecular function of the CLN3 protein has yet to be identified; however, the protein is linked to regulating the lumen pH of the neuronal lysosome, as well as regulating vesicular trafficking [4]. This is significant in Batten Disease patients, such that gangliosides (subtype of neuron sugar residues), cationic amino acids, and other organelle byproducts accumulate in the neuronal cytoplasm when CLN3 is defective [4]. The buildup of cellular waste in neurons prevents the cell from functioning normally, and is believed to cause the symptoms of Batten Disease.
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Symptoms of Disease
Infants develop "normally" following birth until about four to six years in age [1]. Once the first symptom appears, the disease becomes progressively more debilitating. Vision loss is typically the first noticeable symptom [1]. As time progresses, more mild symptoms become noticeable, and later severe symptoms advance quickly. Generally, the severe symptoms will become most noticeable by teenage years [3].
Mild symptoms include [1]:
Mild symptoms include [1]:
- some vision loss
- increased clumsiness
- decreased attentiveness
- total vision loss, seizures
- progressive loss of motor function
- loss of cognitive function
- reduced life expectancy
- dementia
Diagnosis |
Treatment |
The diagnosis of this disease is currently dependent on assays of enzyme activity and molecular genetic testing. This disease has autosomal recessive inheritance, unless there is adult onset, for which, the disease could be autosomal recessive or dominant [3].
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Treatment of Batten Disease is particularly difficult due to the nature of the phenotype. The most prominent course of action is to use preventative genetic testing. This is completed via a blood test. Carrier testing can be administered during prenatal testing if there is family history of deficient enzyme activity. or the mutant CLN3 gene has been identified in the family [3]. Should both parents be a carrier of defected CLN3, they can contact genetic counselors for support.
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Heritability
Batten Disease is an autosomal recessive disorder [1]. This means that both parents must be an unaffected carrier for the disease in order for their child to display symptoms. Patients with juvenile Batten Disease typically do not live long enough to have children; however, there are no studies that show that it is impossible.
Supporting Organizations
Address:
Batten Disease Support and Research Association 2780 Airport Drive, Suite 342 Columbus, Ohio 43219 Toll-Free: (800) 448-4570 Fax: (866) 648-8718 |
Address:
Batten Disease Family Association 209-211 City Road, London, EC1V 1JN Support : 0800-046-9832 [email protected] |
References:
[1] Mathavarajah, S., Mclaren, M. D., & Huber, R. J. (2018). Cln3 function is linked to osmoregulation in a Dictyostelium model of Batten disease. Biochimica Et Biophysica Acta (BBA) - Molecular Basis of Disease,1864(11), 3559-3573. doi:10.1016/j.bbadis.2018.08.013
[2] Batten Disease Fact Sheet. (n.d.). Retrieved from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Batten-Disease-Fact-Sheet
[3] Mole SE, Williams RE. Neuronal Ceroid-Lipofuscinoses. 2001 Oct 10 [Updated 2013 Aug 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
[4] Somogyi, A., Petcherski, A., Beckert, B., Huebecker, M., Priestman, D., Banning, A., . . . Tikkanen, R. (2018). Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis. International Journal of Molecular Sciences,19(2), 625. doi:10.3390/ijms19020625
Images:
Header: https://webvision.med.utah.edu/book/electrophysiology/the-electroretinogram-clinical-applications/
Figure 1: https://ghr.nlm.nih.gov/gene/CLN3#location
Figure 2: https://bdsra.org/cln3-disease-juvenile/
Figure 3: https://en.wikipedia.org/wiki/Batten_disease
Batten Disease Support and Research Association: https://bdsra.org/
BFDa: http://www.bdfa-uk.org.uk/
[1] Mathavarajah, S., Mclaren, M. D., & Huber, R. J. (2018). Cln3 function is linked to osmoregulation in a Dictyostelium model of Batten disease. Biochimica Et Biophysica Acta (BBA) - Molecular Basis of Disease,1864(11), 3559-3573. doi:10.1016/j.bbadis.2018.08.013
[2] Batten Disease Fact Sheet. (n.d.). Retrieved from https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Batten-Disease-Fact-Sheet
[3] Mole SE, Williams RE. Neuronal Ceroid-Lipofuscinoses. 2001 Oct 10 [Updated 2013 Aug 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
[4] Somogyi, A., Petcherski, A., Beckert, B., Huebecker, M., Priestman, D., Banning, A., . . . Tikkanen, R. (2018). Altered Expression of Ganglioside Metabolizing Enzymes Results in GM3 Ganglioside Accumulation in Cerebellar Cells of a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis. International Journal of Molecular Sciences,19(2), 625. doi:10.3390/ijms19020625
Images:
Header: https://webvision.med.utah.edu/book/electrophysiology/the-electroretinogram-clinical-applications/
Figure 1: https://ghr.nlm.nih.gov/gene/CLN3#location
Figure 2: https://bdsra.org/cln3-disease-juvenile/
Figure 3: https://en.wikipedia.org/wiki/Batten_disease
Batten Disease Support and Research Association: https://bdsra.org/
BFDa: http://www.bdfa-uk.org.uk/