Description

• Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare autosomal recessive lysosomal storage disease.
• This neurodegenerative disorder usually presents between ages 2 and 4 years with psychomotor decline, seizures, and vision loss which progress to a vegetative state and death in the 2nd decade of life (1).
• Synonym(s): Jansky-Bielschowsky disease; late-infantile neuronal ceroid lipofuscinosis (NCL); late-infantile Batten disease

Epidemiology

Incidence

• Worldwide reported incidence estimates range from 0.22 to 9 per 100,000 live births (1).
• In the United States, CLN2 occurs in an estimated 2 to 4 of every 100,000 live births.

Prevalence
CLN2 has an estimated prevalence of 0.6 to 0.7 per million inhabitants worldwide.

Etiology and Pathophysiology

• CLN2 is caused by deficiency of the enzyme tripeptidyl peptidase 1 (TPP1), leading to the lysosomal accumulation of an autofluorescent lipopigment with subsequent neuronal degeneration of the hippocampus, cortical interneurons, cerebellum, and thalamocortical neurons (1,2).
• TPP1 cleaves tripeptides from the N-terminus of diverse partially unfolded lysosomal proteins; however, the in vivo substrates of TPP1 are unknown.
• The mechanism by which failure to cleave these N-terminal peptides leads to neuronal death and the clinical manifestations seen in CLN2 is poorly understood.

Genetics

• This disorder is caused by mutations in the TPP1/CLN2 gene located in chromosome 11p15.4 (OMIM 204500).
• The two most common mutations found in patients with CLN2 are c.509-1G>C, a splicing mutation, and c.622C>T (R208X), which results in the introduction of a termination codon prematurely.

General Prevention

• Prenatal diagnosis is an option in patients with family history of CLN2 or known carriers.
• Genetic counseling should be offered to family members and the risk of CLN2 should be assessed for subsequent pregnancies.

Commonly Associated Conditions

• Epilepsy is present in 75% of children with CLN2, usually diagnosed between age 2 and 4 years.
• Perioperative hypothermia secondary to impaired thermoregulation in the setting of autonomic nerve dysfunction is common.
• Cardiac conduction defects, tachyarrhythmias, and sudden cardiac death have been reported.