Ceroid lipofuscinois, neuronal 2, late infantile

Ceroid lipofuscinois, neuronal 2, late infantile
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Ceroid lipofuscinosis, neuronal 2, late infantile (CLN2) is a rare, inherited neurodegenerative disorder that primarily affects children. It is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which are characterized by the accumulation of lipopigments in the body's tissues. These lipopigments are made up of fats and proteins and are named ceroid and lipofuscin.

Genetics

CLN2 is caused by mutations in the TPP1 gene, which provides instructions for producing an enzyme called tripeptidyl peptidase 1. This enzyme is involved in the breakdown of proteins in the lysosomes, which are compartments within cells that digest and recycle different types of molecules. Mutations in the TPP1 gene lead to a deficiency of this enzyme, resulting in the accumulation of undigested proteins and other substances in the lysosomes, which is toxic to cells, particularly neurons.

Clinical Presentation

The symptoms of CLN2 typically begin between the ages of 2 and 4 years. Early signs include:

• Seizures, often myoclonic or generalized tonic-clonic
• Progressive loss of vision due to retinal degeneration
• Decline in motor skills, leading to loss of the ability to walk
• Cognitive decline and speech difficulties

As the disease progresses, children with CLN2 may develop:

• Muscle twitches (myoclonus)
• Ataxia (lack of coordination)
• Behavioral changes

Diagnosis

Diagnosis of CLN2 is based on clinical evaluation, family history, and genetic testing to identify mutations in the TPP1 gene. Additional tests may include:

• Electroencephalogram (EEG) to detect abnormal brain activity
• Magnetic resonance imaging (MRI) to identify brain changes
• Enzyme activity assays to measure TPP1 activity

Management

There is currently no cure for CLN2, and treatment focuses on managing symptoms and providing supportive care. This may include:

• Antiepileptic drugs to control seizures
• Physical therapy to maintain mobility
• Occupational therapy to assist with daily activities
• Speech therapy

In recent years, enzyme replacement therapy with cerliponase alfa has been approved for use in some countries, which may slow the progression of the disease.

Prognosis

The prognosis for children with CLN2 is poor, with most affected individuals losing the ability to walk and speak by late childhood. Life expectancy is significantly reduced, with many individuals not surviving beyond their teenage years.

Research

Ongoing research is focused on understanding the pathophysiology of CLN2 and developing new treatments, including gene therapy and other novel therapeutic approaches.

Also see

• Neuronal ceroid lipofuscinosis
• Lysosomal storage disease
• Genetic disorder
• Neurodegenerative disease