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Neuronal Ceroid Lipofuscinosis 2

Disease Details

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Description: Neuronal ceroid lipofuscinosis 2 (CLN2) is a rare, inherited neurodegenerative disorder characterized by seizures, vision loss, and cognitive decline due to the accumulation of lipofuscins in the body's tissues.
Type: Neuronal ceroid lipofuscinosis 2 (NCL2) is a type of lysosomal storage disorder. The type of genetic transmission for NCL2 is autosomal recessive.
Signs And Symptoms: Signs and Symptoms of Neuronal Ceroid Lipofuscinosis 2 (NCL2):

1. **Developmental Delay**: Children may experience delayed developmental milestones, such as walking and talking.
2. **Seizures**: Often one of the first signs, occurring typically between the ages of 2 and 4.
3. **Vision Loss**: Progressive vision impairment leading to blindness.
4. **Movement Disorders**: Coordination problems, muscle stiffness, and tremors.
5. **Cognitive Decline**: Deterioration in intellectual abilities and dementia.
6. **Behavioral Changes**: Agitation, anxiety, and mood swings.
7. **Motor Skills Regression**: Loss of previously acquired motor skills.

These symptoms typically follow a progressive course, worsening over time.
Prognosis: Neuronal ceroid lipofuscinosis 2 (NCL2), also known as CLN2 disease or late-infantile neuronal ceroid lipofuscinosis (LINCL), is a severe, inherited neurodegenerative disorder. The prognosis for individuals with NCL2 is generally poor, as the disease leads to progressive neurological decline.

Typically, children with NCL2 begin showing symptoms between the ages of 2 and 4, including seizures, loss of motor skills, and visual impairment. As the disease progresses, affected individuals experience cognitive decline, loss of speech, and motor deterioration. Life expectancy is often significantly reduced, with many patients surviving into their teenage years, although some may live slightly longer with supportive care. Advances in treatments like enzyme replacement therapy have the potential to modify the disease course, but the overall prognosis remains serious.
Onset: Neuronal ceroid lipofuscinosis type 2 (CLN2) typically has its onset between the ages of 2 and 4 years.
Prevalence: The prevalence of Neuronal Ceroid Lipofuscinosis 2 (CLN2) is estimated to be approximately 0.46 to 0.56 per 100,000 people. This condition is extremely rare and falls under the category of orphan diseases.
Epidemiology: Neuronal ceroid lipofuscinosis type 2 (CLN2), also known as late-infantile neuronal ceroid lipofuscinosis (LINCL), is a rare, inherited neurodegenerative disorder. It primarily affects children, with symptoms usually appearing between ages 2 and 4.

The estimated prevalence of CLN2 is about 0.1 to 0.2 per 100,000 live births globally. The disease is autosomal recessive, meaning both parents must carry a copy of the mutated gene (TPP1 gene) on chromosome 11 for their child to be affected.

It occurs worldwide, with no particular ethnic or geographical predilection. However, the actual prevalence may vary due to differences in diagnostic capabilities and genetic factors across populations.
Intractability: Neuronal Ceroid Lipofuscinosis 2 (NCL2), also known as CLN2 disease, is considered intractable. It is a rare, inherited neurodegenerative disorder with progressive and severe symptoms that typically result in early death. Despite ongoing research and some advancements in treatments, such as enzyme replacement therapy (ERT) with cerliponase alfa, there is currently no cure for NCL2, and management focuses primarily on symptom relief and supportive care.
Disease Severity: Neuronal ceroid lipofuscinosis 2 (CLN2) is a severe, rapidly progressing neurodegenerative disorder. Most children with CLN2 develop seizures between ages 2 and 4, followed by progressive loss of motor skills, speech, vision, and cognitive function. The disease often leads to premature death in late childhood or early teenage years. The severity of the disease is high, requiring comprehensive and multidisciplinary management for affected individuals.
Healthcare Professionals: Disease Ontology ID - DOID:0110726
Pathophysiology: Neuronal ceroid lipofuscinosis 2 (CLN2) is a neurodegenerative disorder caused by mutations in the TPP1 gene, which encodes the enzyme tripeptidyl peptidase 1 (TPP1). Deficiency in TPP1 leads to the abnormal accumulation of autofluorescent lipopigments, known as lipofuscins, in neurons and other cell types. This accumulation disrupts cellular function and leads to progressive neuronal loss, manifesting as seizures, motor deterioration, vision loss, and cognitive decline.
Carrier Status: Carrier status for neuronal ceroid lipofuscinosis 2 (CLN2) refers to individuals who carry one mutated copy of the TPP1 gene but do not exhibit symptoms of the disease. These carriers have the potential to pass the mutated gene to their offspring. CLN2 is inherited in an autosomal recessive manner, meaning a child would need to inherit two mutated copies (one from each parent) to manifest the disease.
Mechanism: Neuronal ceroid lipofuscinosis 2 (NCL2), also known as CLN2 disease, is a type of Batten disease. It is primarily caused by mutations in the TPP1 gene, which encodes the enzyme tripeptidyl peptidase 1 (TPP1). This enzyme is essential for breaking down specific proteins within lysosomes, the recycling centers of cells.

**Mechanism and Molecular Mechanisms:**
1. **Gene Mutation:** Mutations in the TPP1 gene result in a deficiency or complete lack of functional TPP1 enzyme.
2. **Protein Accumulation:** Without functional TPP1, peptides and other substrates that should be degraded accumulate within lysosomes in neurons and other cell types.
3. **Cellular Dysfunction:** The buildup of these undegraded substrates (such as ceroid and lipofuscin) leads to cellular dysfunction, particularly in neurons.
4. **Neurodegeneration:** The progressive accumulation of storage materials ultimately causes neuron death and leads to the clinical manifestations of the disease, including seizures, motor decline, and vision loss.

Understanding these molecular mechanisms is crucial for developing potential therapies, such as enzyme replacement therapy or gene therapy, aimed at restoring TPP1 function or mitigating the effects of its loss.
Treatment: Neuronal ceroid lipofuscinosis 2 (CLN2) is a rare, inherited neurodegenerative disorder. The primary treatment for CLN2 involves enzyme replacement therapy with cerliponase alfa (Brineura), which is administered directly into the cerebrospinal fluid to replace the deficient tripeptidyl peptidase 1 (TPP1) enzyme. This treatment aims to slow disease progression and improve quality of life. Additional supportive treatments may include anticonvulsants for seizures, physical therapy, occupational therapy, and other symptomatic management as needed. Regular follow-ups with a multidisciplinary team are essential for optimal care.
Compassionate Use Treatment: Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare, inherited neurodegenerative disorder. For CLN2, the primary FDA-approved treatment is cerliponase alfa (Brineura), an enzyme replacement therapy that helps slow the disease progression.

Compassionate use treatment and off-label or experimental treatments may include:
1. **Gene therapy**: Ongoing research is exploring gene therapy approaches to correct the underlying genetic defect.
2. **Stem cell therapy**: Investigated for its potential to repair or replace damaged neurons.
3. **Antioxidants and anti-inflammatory agents**: Sometimes used to manage symptoms and slow disease progression.

Patients should consult their healthcare providers to discuss the potential availability and appropriateness of these off-label or experimental treatments.
Lifestyle Recommendations: For neuronal ceroid lipofuscinosis type 2 (CLN2), a rare and severe neurodegenerative disorder, there are no specific lifestyle recommendations that can halt the disease's progression. However, general management practices can help improve quality of life:

1. **Regular Medical Follow-ups:** Consistent monitoring by healthcare professionals specializing in neurological disorders.
2. **Physical Therapy:** To maintain mobility and manage muscle stiffness.
3. **Occupational Therapy:** To assist with daily activities and promote independence.
4. **Speech Therapy:** To address communication difficulties.
5. **Nutritional Support:** Ensuring a balanced diet to maintain overall health, potentially with the help of a nutritionist.
6. **Adaptive Equipment:** Utilizing wheelchairs, communication devices, and other aids to support daily functioning.
7. **Seizure Management:** Adhering to prescribed antiepileptic drugs and seizure precautions.
8. **Emotional and Psychological Support:** Counseling and support groups for patients and family members to cope with the emotional impact of the disease.

Please consult a medical professional for tailored advice suited to the specific needs of the individual affected by CLN2.
Medication: For Neuronal Ceroid Lipofuscinosis 2 (NCL2), also known as CLN2 disease or late-infantile Batten disease, the FDA-approved medication is cerliponase alfa (Brineura). This enzyme replacement therapy is designed to slow the progression of motor function loss in symptomatic pediatric patients aged 3 years and older with CLN2 disease.
Repurposable Drugs: For Neuronal Ceroid Lipofuscinosis 2 (NCL2), also known as CLN2 disease, some drugs being investigated for repurposing include Cerliponase alfa, which is an enzyme replacement therapy specifically approved for CLN2. Other drugs such as anticonvulsants (e.g., valproic acid and lamotrigine) are also used to manage seizures associated with the disease. However, ongoing research is essential for identifying more effective treatments.
Metabolites: Neuronal Ceroid Lipofuscinosis 2 (NCL2), also known as CLN2 disease, primarily sees the accumulation of autofluorescent lipopigments, specifically lipofuscin, in the neurons and other cell types. This buildup is due to mutations in the TPP1 gene, leading to deficient or absent tripeptidyl peptidase 1 (TPP1) enzyme activity, which disrupts normal cellular metabolism and waste removal processes. Abnormal levels of certain metabolites such as subunit c of mitochondrial ATP synthase may also be observed in affected tissues.
Nutraceuticals: Neuronal ceroid lipofuscinosis 2 (NCL2), also known as CLN2 disease or late-infantile Batten disease, currently has no established nutraceutical treatments. Researchers continue to investigate potential therapies, but there is no conclusive evidence supporting nutraceuticals for NCL2 management.

In terms of nanotechnology, exploratory research is ongoing to develop nanomedicine approaches that may enhance targeted drug delivery or support gene therapy for NCL2. However, these treatments are still in experimental stages and not yet available for clinical use.
Peptides: Neuronal ceroid lipofuscinosis 2 (NCL2) is caused by mutations in the TPP1 gene, which encodes the enzyme tripeptidyl peptidase 1. This enzyme is crucial for breaking down certain peptides within the lysosomes. When TPP1 is deficient or absent, these peptides accumulate, leading to the progressive neurodegenerative symptoms observed in NCL2. Treatment strategies being explored include enzyme replacement therapy to restore TPP1 activity and reduce peptide buildup.