Are there any alternative names?
CLN13 disease, adult, may also be referred to as Adult Kufs Type B disease.
What specifically causes CLN disease?
CLN13 disease is caused by mutations in the CLN13 or Cathepsin F (CTSF) gene, which is found on chromosome 11. The gene was identified as the cause of Adult Kufs Type B in 2012. It is very rare with only 14 known mutations causing CLN13 disease in a small number of individuals.
The CLN13 gene codes for the production of an enzyme called Cathepsin F. This is a lysosomal cysteine protease believed to be involved in intracellular degradation and turnover of proteins and is expressed at a high level in neurons of the cerebral cortex, cerebellum and hippocampus. When it is mutated, the lysosomes cannot recycle material correctly and there is build-up of material inside cells that stops them working properly. Neurons (nerve cells) are particularly vulnerable to the damage caused and, over time, this leads to symptoms associated with CLN13 disease.
How are NCLs inherited?
Most forms of NCL are bi-allelic disorders where the inheritance "autosomal recessive". This is one of several ways that a trait, disorder, or disease can be passed down through families. An autosomal recessive disorder means that both copies of the gene are abnormal (one inherited from each parent) with neither working properly. The parent (or a sibling) carrying only one abnormal gene is healthy because the second copy of the gene is still working. The disease does not depend on the sex of an individual.
What are the chances of inheriting CLN13 disease?
CLN13 disease is inherited as an autosomal recessive disorder, which means that both chromosomes carry mutations in the CLN13 gene. Therefore, both biological parents of a child with this diagnosis will be carriers of the disease but physically unaffected by it.
A child born to parents who both carry the autosomal recessive mutation in the CLN13 gene has a 25% (1 in 4) chance of inheriting the abnormal malfunctioning genes from both parents and developing CLN13 disease. They will have a 50% (1 in 2) chance of inheriting one abnormal gene, which would make them a carrier who is unaffected by the disease. There is a 25% (1 in 4) chance of the child being born with two normal genes and therefore being non-affected (not a carrier).
When it is known that both parents are carriers of the abnormal gene, and a child is already known to be unaffected, we refer to there being a 2 in 3 chance of a child being a carrier. With any pregnancy, the probability of a child inheriting one or both genes from their parents is the same each time, irrespective of any sibling's status.
How is it diagnosed?
Diagnosis of CLN13 disease is challenging due to overlap of symptoms with other disorders. Individuals will probably have been seen by a neurologist because of symptoms such as progressive behavioural abnormalities and dementia. A number of investigations, including a brain biopsy, may have been undertaken to look for the cause of these.
The diagnosis of CLN13 disease is usually made by genetic tests, looking at lots of genes at the same time, all of which are known to cause the same type of symptoms as Batten disease. A blood or saliva sample will be taken to extract DNA from the cells for the test. Genetic testing is recommended to identify the exact mutations or mistakes in the CLN13 gene.
In the past, before the NCL genes were identified, blood or skin cells were looked at using an electron microscope to see the abnormal storage bodies in the cells. These can have characteristic patterns, depending on the type of NCL.
How common is it?
CLN13 disease is very rare with only 22 currently identified throughout the world.
What are the symptoms and how does the disease progress?
Usually, the affected individual appears to be healthy and develop normally until symptoms start. There are various differences in terms of the age of onset and the progression of each genetic variant. Each variant will have a usual age range where symptoms start to appear although individuals may be described as atypical onset if they become symptomatic outside of the normal age range.
Individuals appear to be healthy and develop normally into adulthood. Symptoms usually start around 30 years of age with memory deficits and behavioural changes. As the disease progresses affected individuals develop tremors, bradykinesia (slowness of movement), and extrapyramidal type rigidity. There is no loss of vision associated with CLN13 disease.
There are two children who have been diagnosed with CLN13 disease. Two older adults who developed frontotemporal lobe dementia have been found to carry a mutation in just one copy of the CLN13 gene.
Are there any treatments?
Currently there is no cure for CLN13 disease and therefore specialist symptom management and therapy are essential to assist in maintaining a good quality of life for individuals and their families. Holistic support for parents, siblings and wider family members is extremely important throughout their journey.
Myoclonic jerks (involuntary muscle spasms) are common, though should not be confused with epileptic seizures. They can interfere with rest and sleep as well as being distressing for children and their families. Along with spasticity (unusually tight or stiff muscles), these symptoms can be managed with different medications.
Various professionals including doctors, nurses, physiotherapists, occupational therapists and speech and language therapists should be involved in the care of individuals with CLN13 disease. They will work collaboratively and in conjunction with the family to provide a holistic approach to care.
Support and treatment will be needed for a range of issues including progressive difficulties with chewing and swallowing, constipation, hydration, respiratory function, oral secretions, motor disorder and sleep disturbance. Attention to posture, skin and mouth care is essential and infants will require additional nutritional support that may include consideration of a gastrostomy.
What research is being done?
Research into possible methods for treating the disease is ongoing with current consideration of several possible therapeutic strategies being investigated.
Gene therapy is an experimental treatment where the aim is to introduce a healthy copy of a defective (abnormal) gene into the patient cells. Small molecule therapies are also being investigated using compounds, or drugs, which may mimic the function of the enzyme.
Are there any clinical trials looking into CLN13 disease?
There is currently an observational study, NCT04613089 in Hamburg, Germany, investigating the natural history of CLN13 disease. While not investigating treatments, observational studies are important for future trials as they provide valuable information on how Batten disease progresses over time. If you are considering participating in a clinical trial, please contact us at the BDFA. The information for these clinical trials can be found on: https://clinicaltrials.gov/
What are the genetic considerations?
It may also be possible that there are unaffected siblings who are carriers of the disease and may want to understand how CLN13 disease may affect their family choices. When only one parent is a carrier of the abnormal gene, and the other is non-affected, there is a 50% (1 in 2) chance that any child will be an unaffected carrier.
If siblings are considering having children, they can access specialist advice and support from their local clinical genetics service following a referral from their GP. Prenatal testing may be possible in the early stages of any future pregnancy.
Is support available to families?
As soon as possible following a diagnosis of CLN13 disease, families should be offered support from various professionals attached to their local health, social, educational services and the BDFA Support and Advocacy team. Ideally a "Team Around the Individual" will be formed, with one of the professionals appointed as a Keyworker for the family.
The individual's needs should be discussed with the family and assessed by the team. The team will work together to ensure that the family receive the on-going care and support they need and that their choices are taken into account.
An individual and family's needs will inevitably change as the disease progresses. As such, it is often helpful if a clear process for regular planned reviews is identified and that a system is established for enabling additional reviews as and when they are deemed necessary. As the rate or pattern of the progression of the disease for each individual can vary, an individualised plan of care and support is essential.
How can families manage the financial challenges?
Caring for an individual with CLN13 disease will bring additional financial challenges. It is vital that families are well informed about the full level of economic assistance available and the support that they are entitled to. They may well need help and guidance in accessing benefits and other sources of assistance. The professionals and services supporting the family should provide advice and guidance. The BDFA can also support families with these issues in various ways, the Small Grants Scheme being one example.
What are the practical implications for the family?
As the disease progresses, specialist equipment and aids will become necessary, and this is another area where the family will need help. Items are likely to include specialist seating, buggies/wheelchairs, bathing and toileting aids, hoisting equipment and a specialist bed/mattress. Professionals will play a key role in ensuring that these and other items are provided in a timely manner following proper assessment of the individual's needs.
It is likely that changes will be needed in the home environment to enable the family to appropriately care for an individual with CLN13 disease. These may include installing ramps, widening doorways and providing suitable floor surfaces. A purpose-built wet room with a specialist bath or shower is commonly needed and there are various other aspects that will require consideration.
There are grants and funds available to ensure that the work involved is affordable. An occupational therapist will consult on all aspects of any adaptations and assist the family in undertaking this process.
Will there be an impact on the individual's education?
Education is likely to have been completed before symptoms start. However, there will be an impact on their ability to work and there will be many aspects that require consideration and significant assistance from those around them.
In what other ways can families be supported?
The realities of caring for an individual who has CLN13 disease can place enormous strain on a family, both physical and emotional. It will impact upon all members in numerous ways and so being made aware that support is available to groups and individuals to help with the challenges that will be faced is important. This support extends to wider family members and step-relatives.
There are several options to consider should families wish to explore ways of maximising the limited time available to share with their loved one. Contacting a charitable wish granting organisation may lead to them being able to create some valuable and significant memories.
It may also be appropriate for a referral to be made to a local hospice service, as this can offer an additional experienced and skilled source of holistic support.
Contributors- BDFA Head of Scientific Affairs, Professor Paul Gissen, Clinical Professor of Paediatric Metabolic Medicine, Professor Sara Mole, Professor of Molecular Cell Biology, Genetics & Genomic Medicine.
Some of the information contained in this leaflet is based upon chapters in "The Neuronal Ceroid Lipofuscinoses (Batten Disease) 2nd Edition" by Mole, Williams & Goebel (Eds), Oxford University Press 2011, and is used with permission.