What Is CLN2 Disease?
CLN2 disease causes progressively worsening problems with vision, movement, and thinking ability. Each type of NCL is classified as "CLN," meaning ceroid lipofuscinosis, neuronal, followed by a subtype number that distinguishes it based on its genetic cause. The symptoms of the disease manifest between ages 2 and 4. Early symptoms may include recurrent seizures, difficulty coordinating movements, muscle twitches, and vision loss. Motor skills that are affected include sitting and walking, as well as speech development. Developmental regression, worsening intellectual disability, and behavioral problems may follow.
While some children with CLN2 disease may not show symptoms until later in childhood, they usually have a less severe form of the disease, with milder symptoms but more severe ataxia. These individuals have a shorter life expectancy but tend to survive into adulthood.
What Causes CLN2 Disease?
TPP1 gene mutations cause CLN2 disease which provides instructions for producing the enzyme tripeptidyl peptidase 1. Protein is broken down by this enzyme and thus plays a crucial role in breaking down protein fragments in lysosomes, which are responsible for digesting and recycling various types of molecules. These mutations lead to an incomplete breakdown of peptides. This incomplete breakdown results in the accumulation of peptides and other substances in lysosomes throughout the body, particularly in nerve cells. This accumulation causes cell damage and eventually leads to cell death. CLN2 disease is characterized by the progressive death of nerve cells in the brain and other tissues, resulting in the signs and symptoms of the disease.
Interestingly, individuals diagnosed with CLN2 disease later in childhood may have mutations that allow for producing a small amount of functional enzyme. In such cases, protein function is higher than in individuals diagnosed earlier in childhood, and it takes longer for substances to accumulate in lysosomes and damage nerve cells. This finding suggests that disease onset and progression may be influenced by the level of functional enzyme produced by the TPP1 gene.
Enzyme activity measurement and skin or tissue sampling are used as diagnostic tools in identifying CLN1 and CLN2 type Batten disease, helping to confirm or rule out the condition's presence by assessing the activity of specific enzymes in the patient's body.
What Are the Other Names For CLN2 Disease?
Other names for this condition include:
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Late-infantile Batten disease.
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Jansky-Bielschowsky disease.
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Late-infantile neuronal ceroid lipofuscinosis (LINCL).
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Neuronal ceroid lipofuscinosis, late-infantile.
How Is CLN2 Disease Managed in Pediatrics?
There is currently no cure for CLN2 disease, and disease management is focused on providing supportive care to improve quality of life and alleviate symptoms. Management goals and strategies are consistent among experts globally and guided by pediatric palliative care principles. A multidisciplinary approach is critical for optimal patient care.
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Clinical Management- Clinical management involves pharmacological management, dietary interventions, and physiotherapy. Children with CLN2 disease typically receive palliative care, which aims to alleviate pain, manage symptoms, and maximize the quality of life. Pharmacological management includes using anticonvulsants to control seizures, common in CLN2 disease, and medications to manage other symptoms such as sleep disturbances and anxiety.
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Dietary Management- Dietary interventions are also crucial in managing CLN2 disease. Children may require assistance with feeding and may need specialized formulas or feeding tubes to ensure adequate nutrition. Dietary modifications may sometimes be necessary to manage gastrointestinal symptoms, such as reflux and constipation.
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Physiotherapy- It helps improve the quality of life of children with CLN2 disease. Physiotherapeutic goals aim to support children's participation in daily activities by promoting their ability to communicate, eat and drink, and maintain mobility for as long as possible. Early intervention and continued support are essential to help children express their thoughts and wishes.
Physiotherapeutic interventions also focus on maximizing functional independence and daily participation, reducing the risk of complications, and enabling children to maintain upright positions. Education on appropriate supportive body positioning for safe swallowing and the use of medical aids such as standing devices are critical components of treatment. Functional goals are set with the patient's families, and they are counseled on treatment and care options throughout the disease.
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Maintaining Upright Positions - In children with CLN2 disease, physiotherapy management for upright positions is mandatory. Children with CLN2 disease may experience muscle weakness and spasticity, leading to standing, sitting, and walking difficulties. Physiotherapists work with the child and their family to develop a plan for maintaining upright positions tailored to their needs and abilities.
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Standing Devices or Therapy Chairs - One approach that may be used to maintain upright positions is using standing devices or therapy chairs. These devices can support the child while they are in a good position, which can help improve circulation, reduce the risk of joint contractures, and improve respiratory function. Standing devices may be used for short periods throughout the day to increase the time the child spends upright gradually.
Physiotherapists may also work with the child and their family to develop exercises that can help strengthen the muscles used for standing, sitting, and walking. These exercises may include stretching, range of motion, and resistance training. In addition, physiotherapists may educate parents and caregivers on proper body positioning and techniques for assisting the child with standing and walking.
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Body Positioning During Meals - Children with CLN2 disease may experience difficulties with swallowing, which can lead to an increased risk of aspiration and respiratory complications. Proper body positioning during meals and feeding can help reduce this risk.
Physiotherapists work with the child and their family to develop a plan for supportive body positioning during meals and feeding. This may include positioning the child upright. The child may be placed in a special feeding chair or seat, with appropriate supports to maintain their position.
Conclusion:
The ultimate aim is to provide patients with the best possible quality of life as the disease progresses. Initially, the focus is on maintaining function, but as the disease advances, the focus shifts to maintaining the quality of life. A multidisciplinary approach is critical to providing optimal care to patients with CLN2 disease. This approach involves a team of healthcare professionals who work together to manage the patient's physical, psychological, and emotional needs.
