Acknowledgement of CLN2 Disease (Late-Infantile Neuronal Ceroid Lipofuscinosis) has not been added yet.

CLN2 disease is estimated to occur in 1 in 200,000 live births globally. It affects both males and females equally and is observed in various ethnic and racial groups. In some populations, such as in Newfoundland, Canada, the incidence is higher, estimated to occur in 9 out of 100,000 children born in this region.

Name	Abbreviation
	Late-Infantile Neuronal Ceroid Lipofuscinosis (LINCL), TPP1 Deficiency, JNCL (Juvenile Neuronal Ceroid Lipofuscinosis) JNCL is typically associated with CLN3, Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), Jansky–Bielschowsky Disease
Late-Infantile Neuronal Ceroid Lipofuscinosis	LINCL
TPP1 Deficiency
Juvenile Neuronal Ceroid Lipofuscinosis, though JNCL is typically associated with CLN3	JNCL
Neuronal Ceroid Lipofuscinosis Type 2	CLN2
Jansky–Bielschowsky Disease

CLN2 disease is caused by mutations in the TPP1 gene (also known as CLN2) located on chromosome 11p15. This gene encodes the enzyme tripeptidyl peptidase 1 (TPP1), which is crucial for breaking down proteins within intracellular compartments known as lysosomes. Deficiency in TPP1 activity leads to the accumulation of an autofluorescent storage material called ceroid lipofuscin within cells, disrupting cellular function particularly in neurons, leading to the clinical manifestations of the disease.

CLN2 disease follows an autosomal recessive inheritance pattern (see RareShare Guide on Genetic Inheritance). This means that an affected individual must inherit two copies of the mutated TPP1 gene, one from each parent, to develop the disease. It is possible for individuals to be born with a lower than normal functioning TPP1 gene or produce the enzyme at lower levels and only experience symptoms and become diagnosed with CLN2 later in life.

Symptoms of CLN2 disease typically appear between the ages of 2 and 4 years. The disease progression is characterized by:

1. Early Stage (typically ages 2-4):

   • Recurrent seizures (often the first noticeable symptom)

   • Language delay or regression

   • Ataxia (loss of coordination and balance)

2. Middle Stage (typically ages 4-6):

   • Myoclonus (involuntary muscle jerks)

   • Progressive vision loss

   • Cognitive decline and loss of previously acquired skills

   • Speech difficulties progressing to loss of speech

   • Motor decline, leading to difficulty walking

3. Late Stage (typically ages 6 and older):

   • Complete loss of motor function

   • Blindness

   • Severe cognitive impairment

   • Dysphagia (difficulty swallowing)

The initial diagnosis of CLN2 disease is often delayed due to the non-specificity of early symptoms. A definitive diagnosis of CLN2 disease typically involves a combination of clinical evaluation, enzyme activity assays and genetic testing:

• Clinical Evaluation: Observation of characteristic symptoms and disease progression.

• Enzyme Activity Assay: Measurement of TPP1 enzyme activity in leukocytes or fibroblasts. A significant reduction or absence of TPP1 activity indicates CLN2 disease.

• Genetic Testing: Identification of mutations in the TPP1 gene confirms the diagnosis. Genetic testing can also be used for carrier detection and prenatal diagnosis.

• Diagnostic Tests:

• Electroencephalogram (EEG): Detects abnormal brain activity, which is common in patients with CLN2 disease.

• Magnetic Resonance Imaging (MRI): Reveals brain atrophy and other structural abnormalities.

Electron Microscopy: Identifies characteristic storage material (lipofuscin) in biopsied tissues.

Diagnostic tests of CLN2 Disease (Late-Infantile Neuronal Ceroid Lipofuscinosis) has not been added yet

There is no cure for CLN2 disease. Treatments focus on managing symptoms and slowing disease progression:

• Enzyme Replacement Therapy (ERT): Cerliponase alfa (Brineura) is an FDA-approved treatment that involves the administration of recombinant TPP1 enzyme directly into the cerebrospinal fluid to slow disease progression.

• Symptomatic Treatments:  

  • Antiepileptic Drugs (AEDs): Used to manage seizures.

  • Physical and Occupational Therapy: Helps maintain motor function and improve quality of life.

  • Speech Therapy: Assists with communication challenges.

  • Nutritional Support: May include gastrostomy tube feeding in later stages.

• Supportive Care: 

  • Management of respiratory complications, and other symptomatic treatments.

  • Psychosocial support of families to cope with social and emotional challenges.

  • Palliative care to improve comfort and quality of life.

Emerging Therapies:  Gene therapy approaches are under investigation.

The prognosis for CLN2 disease is generally poor. Most children with CLN2 disease lose their ability to walk and speak by late childhood and often succumb to the disease in their teenage years. Later onset of this disease generally indicates a better prognosis as the individual expresses the tripeptidyl peptidase 1 protein but in smaller quantities. The introduction of enzyme replacement therapy offers hope for slowing disease progression, extending life expectancy and improving the quality of life for patients.

Tips or Suggestions of CLN2 Disease (Late-Infantile Neuronal Ceroid Lipofuscinosis) has not been added yet.

1. CLN2 Family.com: CLN2 family.com.

2. Brineura (Ceroliponase alpha):  Brineura.

3. Williams, R. E., & Mole, S. E. (2012). New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses. Neurology, 79(2), 183-191.

4. https://medlineplus.gov/genetics/condition/cln2-disease/