CLN2 Disease

Neuronal Ceroid Lipofuscinosis Type 2 (CLN2)

CLN2, a form of Batten disease, is a rapidly progressing childhood neurodegenerative disease that causes seizures, dementia and loss of vision.^1,2

^{EU-CLN2-00088 December 2021}

What is CLN2 Disease?

CLN2 is a childhood neurodegenerative disease characterised by language delay, seizures, loss of motor function, dementia, blindness and early death.¹ It is one of the most common forms of neuronal ceroid lipofuscinosis, a group of inherited disorders collectively known as Batten disease, however it is very rare, affecting fewer than 1 in 100,000 live births in most studied populations.^1-3 CLN2 disease is a type of lysosomal storage disorder, in which a deficiency in the enzyme tripeptidyl peptidase 1 (TPP1) causes ceroid lipofuscin to build up in nerve cells.^1,3 This is associated with degeneration in the brain and eyes by an as yet unknown mechanism.³

CLN2 is an autosomal recessive disease,¹ which means that if both parents are carriers of an abnormal TPP1 gene, each time they have a child, there is a one in four chance of that child having CLN2 disease. Families caring for a child affected by CLN2 disease must cope with many difficult emotional and practical challenges, and can experience stress, loss of sleep, lower life satisfaction and a significant financial burden.²

Symptoms of CLN2 Disease

For around 85% of CLN2 patients, the devastating manifestations of the disease follow a predictable course.^1,3 The most common first symptoms are language delay and seizures, which typically begin between the ages of two and four years.¹ This is followed by a period of rapid deterioration in cognitive and motor functions, leading to the loss of speech and movement by about the age of six.¹ Children with CLN2 disease experience developmental regression and worsening dementia,⁴ as well as becoming blind by the time they are ten years old.¹ Patients become wheelchair-bound and dependent on caregivers, and usually die in late childhood or early adolescence.³ In some atypical cases, CLN2 patients may experience earlier or later symptom onset, varied symptoms, and/or slower disease progression.¹

Diagnosing CLN2 Disease

Early diagnosis of CLN2 disease is critical for patients and their caregivers, allowing early initiation of disease-specific care, reducing the risk of inappropriate medications, and enabling families to make informed decisions.¹ Identifying CLN2 early is challenging due to lack of disease awareness and because the initial symptoms can occur in other, more common conditions.^1,3 In children suspected of having CLN2 disease, the disorder can be diagnosed by demonstration of TPP1 enzyme deficiency and/or genetic testing to detect changes in the TPP1 gene.¹ In order to avoid cases being missed, it is essential that clinicians keep CLN2 disease in mind, and that hospitals test for CLN2 when a child presents with seizures and language delay.³ Historically, most children with CLN2 disease have been diagnosed at around five years of age when substantial loss of function has already occurred.¹ Active disease awareness and increased access to diagnostic programmes are reducing the delay in diagnosis.⁵ As large-scale gene panels (which test for multiple disease mutations at once) become increasingly available, the key to early diagnosis may lie in prompt use of these next-generation techniques in patients with unexplained epilepsies or other symptoms of developmental regression, rather than waiting for a clear-cut clinical picture suggesting CLN2 disease.³

Managing CLN2 Disease

Because of the wide range of symptoms experienced by children with CLN2 and the complexity of their clinical needs as the disease rapidly progresses, a multidisciplinary approach is advocated to manage patients and support their families.^1,3 Earlier on, the aim is to keep children functioning for as long as possible, particularly in terms of movement and communication.¹ Understanding of CLN2 is growing and treatment is based on managing clinical signs and symptoms as well as addressing the underlying cause of the disease.³