Neuronal ceroid-lipofuscinosis type 2 (NCL2)


Neuronal ceroid-lipofuscinosis type 2 (NCL2; MIM #204500) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the TPP1 gene which encodes the lysosomal enzyme tripeptidyl peptidase. NCL2 is one of at least eight genetically distinct diseases associated with the NCL disease spectrum. NCL2 is generally referred to as late-infantile NCL (LINCL) due typical onset of symptoms between the ages of 2 and 4 years. Variant forms of LINCL (vLINCL) have been reported to be caused by mutations in the CLN1, CLN5, CLN6, CLN7 and CLN8 genes. Clinical features of LINCL are normal development until the onset of seizures, ataxia and myoclonus between 2 and 4 yrs. LINCL usually progresses with visual loss (by 5-6 yrs), chair bound by 4-6 yrs with poor prognosis. The differential diagnosis of NCL2 from the other NCL types is based on age of onset, clinical phenotype, ultra structural characterisation of the storage material and TPP1 enzyme levels. A clinical diagnosis of NCL2 is confirmed biochemically by loss of tripeptidylpeptidase I (TPP1) enzyme activity in leucocytes and fibroblasts or accumulation of auto fluorescent lipopigment with a curvilinear profile in neurones and other cell types.

Also known as

Late infantile Batten disease; Jansky-Bielschowski disease, CLN2

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When requesting this test please use the referral form provided. Please also refer to any additional information provided for this test.

Additional information

Clinically affected patients should, wherever possible, have their diagnosis confirmed by analysis of TPP1 enzyme activity in leucocytes and fibroblasts. This should be arranged locally or with the Enzyme Unit, Great Ormond Street Hospital. Biochemically confirmed patients can be referred for mutation analysis. If the necessary patient samples are unavailable genetic testing can be undertaken in the parents of an affected child. TPP1 (11p15) consists of 13 exons. The two most common mutations are c.509-1G>C (~33% of LINCL chromosomes) and p.Arg208X (~26 % of LINCL chromosomes). Other disease causing mutations are family specific and found throughout the gene. Level 1 Mutation Analysis: Detection of recurrent mutations c.509-1G>C and p.Arg208X in exon 6 by direct sequencing analysis. Level 2 Mutation Analysis: Direct sequencing of all 13 coding exons and intron-exon boundaries.

Sending address

Rare & Inherited Disease Laboratory
London North Genomic Laboratory Hub
Great Ormond Street Hospital for Children
Levels 4-6 Barclay House
37 Queen Square

Laboratory service


Sample requirements

1ml EDTA neonates, 5ml EDTA adults

Reference range

Not applicable

Turnaround time

Common mutations - 20 days; gene screen - 40 days

Disease / group



Upon request

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Prenatals must be arranged in advance, through a Clinical Genetics department if possible.


The Genetics Laboratories provide an extensive range of Cytogenetics and Molecular Genetics diagnostic testing services.

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