Originally posted at https://medium.com/@sukantkhurana/what-is-battens-disease-bee186d78eee
Batten’s disease, described in 1903 after a British paediatrician named Frederick Batten, is one of the most unfamiliar, fatal, and inherited disorder of the nervous system which generally occurs in childhood.
Batten’s disease is referred to as the juvenile form of NCL (Neuronal ceroid lipofuscinosis). The human hereditary ceroid-lipofuscinosis are a group of autosomally recessive inherited diseases which is caused by accumulation of autofluorescent lysosomal storage bodies in the cells and neuronal degeneration of nervous system. (1)
Batten’s disease has been categorized as a fatal disease occurring in every 2 to 4 of every 100,000 living United states population. The symptoms of this disease becomes evident between 5 to 15 years of age. Batten’s disease is more common in Finland, Sweden and other parts of Northern Europe including Canada. There are cases still not known in the Island of Ireland (2) (3)
DIFFERENT FORMS OF BATTEN’S DISEASE
Infantile NCL — before age 2.
Late infantile NCL — between 2 to 4 years of age, normal life span 8 to 12 years .
Juvenile NCL- between ages 5 and 8.
Adult NCL — begins before age 40.
SIGNS AND SYMPTOMS
Early signs of this disease is not that distinct ranging from personality changes, slow paced learning, cognitive decline and clumsiness.
Progressive loss of vision with macular degeneration, damage to optic nerves and abnormal accumulation of colored pigment on the retina (retinitis pigmentosa)
Children often lose their eyesight by age 10 (4)
With increasing age, symptoms of dementia become evident and motor abnormalities is pronounced similar to that of Parkinson’s disease.
Muscular spasms, speech disturbances, paralysis of all four limbs ( quadriparesis) , mental disturbance including hallucinations and anxiety becomes common.
Batten’s disease is mainly caused due to mutation of the CLN3 gene which is situated on the short arm (p) of the chromosome number 16.
CLN3 gene basically provides instruction to produce a protein called battenin. This protein is located in the lysosomes and the endosomes. The function of this protein is not well defined. (5)
Researchers suspect the fact that Batten’s disease is caused by an unknown alteration in the cell due to which the body is not able to recycle or break down fats and the proteins and sugars associated with it and hence they form lipopigments which gets accumulated in the nerves and the brain cells are affected. (6)
Diagnosis of batten’s disease ensures a detailed patient history because many at times, this disease is mistaken for epilepsy , Schizophrenia or any other mental retardation.
Vision loss is the very first sign that can be recognized. Electroretinography (ERG) can be performed to test the retina’s electrical response to light stimulation and can be used to detect pigmentary degeneration or optic nerve damage.
Increased amount of dolichol ,a long chain unsaturated organic compound in urine can confirm this disease. (7)
Biopsy(sample of tissue from skin) is done to confirm deposits in skin cells especially from sweat glands
Computed Tomography (CT) or MRI testing can be done to confirm the areas of the brain that are decaying or “atrophic”.
DNA Analysis:If the families are known where the mutation of the CLN3 gene has occurred, DNA Analysis can be used to confirm the prenatal diagnosis. DNA Analysis can be used to detect unaffected carriers of this disease for genetic counselling. (8)
Treatment related to Batten’s disease is yet unknown but some current ongoing studies may prove to be beneficial.
Use of anticonvulsant drugs like Valproate and Lamotrigine can be used to control seizures which costs around $ 80 for thirty 100 mg tablets. (9)
Physical and occupational therapy can help the patients.
Hematopoietic Stem cell treatment may be beneficial though not recommended.
Genetic counselling is highly recommended.
CASE STUDIES /REPORTS
Bone marrow transplantation in Batten’s disease- A patient received bone marrow transplantation and the effect on the lymphocytes and the cells in the skin was monitored through an electron microscope for a period of 9 months. So, bone marrow transplantation did not prove to be much beneficial but might prevent or halt the onset of the clinical symptoms .(10)
Batten’s disease in West of Scotland( 1974–1995)- 12 children were diagnosed with neuronal ceroid lipofuscinosis (NCL) in West of Scotland. Out of them 5 or 6 cases showed granular osmiophilic deposits (GROD) rather than fingerprint inclusion bodies when measured through an electron microscope.Four of these five cases also failed to portray vacuolation of lymphocytes. (11)
Evaluation of patients from Turkey (1999)- 36 patients (16 girls and 20 boys) were taken for evaluation . Out of these, 3 patients were classified as infantile NCL, 11 were late infantile NCL, 5 were juvenile type NCL, and 17 were Turkish variant NCL. The Turkish variant NCL showed a severe case regarding seizures and EEG showed abnormal features with an occipital spike. Researchers found out that this disease is quite frequent in Turkey due to high rates of consanguineous marriages. (12)
RECENT CASE STORY OF A YOUNG PATIENT
Born in 2007, Jurica was a young patient from Siberia and she was admitted to Beijing Puhua International Hospital for stem cell treatment for Batten’s disease.
“Before Stem cell treatment, Jurica’s spasms lasted for several minutes. She had slow involuntary movements of both hands.
She was unable to pronounce simple words like “Mom” and “Ah” and her pronunciation was poor. She was unable to see well. She even could not maintain herself in a sitting position.
After her stem cell treatment, her sleeping improved and could control her tongue better and could grip things with better strength and motor control.” (13)
CURRENT ONGOING STUDIES AND RESEARCH
Department of Genetic Medicine at Weill Cornell Medical College in New York City- Conducting a gene therapy research on the CLN2 gene. The basic purpose of this research is to see whether gene transfer surgery in which an experimental drug named as AAVrh.10CUhCLN2 is introduced to the brain and to check out whether this process will slow down the progression of this disease.(14)
University Of Rochester Medical Center- Conducting a clinical trial to study whether mycophenolate (CellCept) is safe and can be tolerated by young patients suffering from Juvenile Neuronal Ceroid Lipofuscinosis. (14)
National Institute Of Health (NIH)- Declared in 2013, a new potential drug has been invented from hydroxylamine called NtBuHA which has been tested in mice with Batten’s disease and was found to increase the lifespan of the animal. Researchers hope that this drug will be useful to treat infantile Batten’s Disease. (15)
Food and drug Administration (FDA)- published in April 2017, FDA has approved Brineura (Cerliponase alfa) as a treatment for Batten’s disease.Brineura is administered to the cerebrospinal fluid by infusion which lasts upto 4.5 hours. This drug has been reported to have certain side effects.(16)
SOCIAL MEDIA EXPOSURE /ORGANIZATIONS
1175 Dublin Road.
Columbus, OH 43215 USA
Toll-free: (866) 648–8718
Children’s Brain Disease Foundation [A Batten Disease Resource]
Parnassus Heights Medical Building, Suite 900
San Francisco, CA 94117
6033 West Century Blvd Suite 350
Los Angeles, CA 90045 USA
Batten’s disease is not contagious but unfortunately not preventable. Till date it has always been fatal. In most cases affected individuals become bedridden and unable to communicate and generally results into a life-threatening condition by late twenties , but recent studies and research have definitely proved to be beneficial.
1. Neuronal ceroid lipofuscinosis (http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-4547(19990815)57:4%3C551::AID-JNR15%3E3.0.CO;2-R/full)
2.overview of batten’s disease
4.loss of vision-(https://www.ncbi.nlm.nih.gov/pubmed/26748992)
5.CLN3 gene(https://ghr.nlm.nih.gov/gene/CLN3#normal function)
6.Mutation in CLN1,CLN2,CLN3 gene
7. Increased dolichol
8.Genetic counselling/gene review-
10. Bone marrow transplantation-
11.case study in West Scotland(https://www.ncbi.nlm.nih.gov/pubmed/9266550)
12. Case study in Turkey (https://www.ncbi.nlm.nih.gov/pubmed/15074367)
13. Case story of a Siberian girl
15. National Institute Of Health https://www.nih.gov/news-events/news-releases/nih-researchers-identify-candidate-drug-treat-batten-disease
16. Food and Drug Administration http://www.news-medical.net/news/20170427/FDA-approves-first-drug-for-treating-rare-form-of-Batten-disease.aspx
17.Juvenile ceroid lipofuscinosis https://www.ncbi.nlm.nih.gov/medgen/155549
18.Stem Cell Treatment– http://www.neurology.org/content/57/8/1411
19. Different forms of Batten’s disease- http://www.battens.org.au/what-are-forms-ncl
Dr. Sukant Khurana runs an academic research lab and several tech companies. He is also a known artist, author, and speaker. You can learn more about Sukant at www.brainnart.com or www.dataisnotjustdata.com and if you wish to work on biomedical research, neuroscience, sustainable development, artificial intelligence or data science projects for public good, you can contact him at firstname.lastname@example.org or by reaching out to him on linkedin https://www.linkedin.com/in/sukant-khurana-755a2343/.