Therefore, when patients initially present to clinic, CLN2 disease is not often suspected. Progression of CLN2 disease is often rapid (PMID: 22832778 ). [invitae.com]

Diagnostic methods The diagnostic strategy for patients presenting with LINCL should include enzymatic testing for deficiencies in palmitoyl-protein thioesterase 1, tripeptidyl-peptidase 1 and cathepsin D, present in patients with PPT1, TPP1 and CTSD [orpha.net]

Results: The present patient was a 4-year-old girl who presented at 2 years and 10 months old with seizures followed by ataxia, regression of skills, and eventual visual decline. TPP1 enzyme activity was below normal for age. [atm.amegroups.com]

• Plethora

  This unique life cycle provides a plethora of phenotypes for study which are essentially readouts of the underlying signalling pathways [12]. Dictyostelium contains homologues for 11 of the 13 NCL genes. [mdpi.com]

• Formication

  To activate the inactive recombinant CLN2 proenzyme secreted by the cells, 10-μL samples (undiluted or diluted two-, four-, or eightfold in phosphate-buffered saline) were mixed with 20 μL of 150 mmol/L NaCl-1 g/L Triton X-100-50 mmol/L formic acid/sodium [clinchem.aaccjnls.org]

• Flushing

  After the infusion, the device is cleared with a flushing solution. The half-life of cerliponase alfa in cerebrospinal fluid is about seven hours and the enzyme is probably cleared by hydrolysis. [nps.org.au]

• Progressive Loss of Vision

  […] of vision Progressive vision loss Progressive visual impairment Slowly progressive visual loss Vision loss, progressive Visual loss, progressive [ more ] 0000529 Retinal degeneration Retina degeneration 0000546 Seizures Seizure 0001250 Undetectable electroretinogram [rarediseases.info.nih.gov]

• Onset at 2 to 4 Years

  Late infantile with CLN2 mutation manifests with onset between 2 and 4 years and symptoms of epilepsy, cognitive decline, ataxia, visual failure, and death in between 9 and 18 years. [pediatricneurosciences.com]

  Patient 467–1 was an outlier with a juvenile disease onset at 8 years of age. Patients with CLN2 usually present between 2 and 4 years of age. [ajnr.org]

• Delayed Speech and Language Development

  speech and language development Deficiency of speech development Delayed language development Delayed speech Delayed speech acquisition Delayed speech development Impaired speech and language development Impaired speech development Language delay Language [rarediseases.info.nih.gov]

• Gait Ataxia

  As the disease progressed, he developed progressive vision loss, gait ataxia, action myoclonus, and epilepsy. Electroencephalogram revealed generalized sharp and slow wave discharges with background slowing. [annalsofian.org]

• Pendular Nystagmus

  Pendular nystagmus was present. Other cranial nerve examination was normal. Tone and power was normal in all the four limbs. Reflexes were brisk and release signs in the form of palmomental, grasp, snout, pout reflex were present. [annalsofian.org]

FORM (PNW) PERIPHERAL NERVE WORKUP FORM (PNW) The Peripheral Nerve Workup Form (PNW) has to be filled out at the time a new patient is enrolled into the PNRR study. [healthdocbox.com]

• Photoparoxysmal Response

  The most characteristic finding on electroencephalogram ( EEG ) is the finding of photoparoxysmal responses to low frequency (1-2 Hz) intermittent photic stimulation. However, this finding may be absent in some patients. [invitae.com]

• Generalized Sharp-and-Slow-Waves

  Electroencephalogram revealed generalized sharp and slow wave discharges with background slowing. [annalsofian.org]

• Pseudomonas

  Cloning, nucleotide sequence, and expression of an isovaleryl pepstatin-insensitive carboxyl proteinase gene from Pseudomonas sp. 101. J Biol Chem 1994 ; 269 : 26518 -26524. ↵ Sohar I, Sleat DE, Jadot M, Lobel P. [clinchem.aaccjnls.org]

Undesirable or hypersensitivity reactions related to Brineura treatment, including fever, vomiting, and irritability, may occur during treatment and as late as 24 hours after infusion. [biomarin.com]

Management and treatment There is no curative treatment. [orpha.net]

Has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions. [drugs.com]

Prognosis The prognosis is poor with most children becoming severely disabled by mid-childhood. Most patients do not survive to reach adulthood. The documents contained in this web site are presented for information purposes only. [orpha.net]

LINCL usually progresses with visual loss (by 5-6 yrs), chair bound by 4-6 yrs with poor prognosis. [labs.gosh.nhs.uk]

[…] with early deaths while juvenile and adult onset forms have a relatively better prognosis. [annalsofian.org]

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 [unboundmedicine.com]

Etiology LINCLs are transmitted in an autosomal recessive manner and mutations in the following genes may result in LINCL with a classic and/or variant phenotype: PPT1 (designated CLN1 ; 1p32), TPP1 (11p15; designated CLN2 and responsible for the majority [orpha.net]

Precise pathogenesis and etiology of this group of diseases remain obscure. [accesspediatrics.mhmedical.com]

Summary Epidemiology LINCLs have been reported in populations with diverse ethnic origins with the highest prevalence being reported in Finland (around 1/385,000), estimates of below 1/1,000,000 in other Scandinavian counties and an annual incidence at [orpha.net]

The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland. Clin Genet. 2008 Sep;74(3):213-22. doi: 10.1111/j.1399-0004.2008.01054.x. Epub 2008 Aug 4. Schulz A, Kohlschütter A, Mink J, Simonati A, Williams R. [ghr.nlm.nih.gov]

Relevant External Links for CLN6 Genetic Association Database (GAD) CLN6 Human Genome Epidemiology (HuGE) Navigator CLN6 Atlas of Genetics and Cytogenetics in Oncology and Haematology: CLN6 No data available for Genatlas for CLN6 Gene Mutations in CLN7 [genecards.org]

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 [unboundmedicine.com]

[…] settings where the test may be helpful Evaluation of patients with clinical presentations suggestive of neuronal ceroid lipofuscinoses (NCL) Aids in the differential diagnosis of infantile and late infantile NCL Clinical Information Discusses physiology, pathophysiology [mayomedicallaboratories.com]

There were 14 cases where pathophysiological findings suggested LINCL but the specimens had detectable pepinase activity and there were no mutations found. [clinchem.aaccjnls.org]

Accumulation of these proteins and lipids prevent the cells from functioning as they should. 2.2 CLN2 progresses rapidly and predictably from presentation in late infancy to death by early adolescence. [nice.org.uk]

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. [unboundmedicine.com]

Cerliponase alfa may slow the decline, but it does not stop the loss of brain cells as MRI showed decreasing grey matter in the treated children.1 Longer term follow-up will be needed to see if cerliponase alfa prevents blindness or improves quality of [nps.org.au]

The levels of impairment defined in the table after 369.9 are based on the recommendations of the WHO Study Group on Prevention of Blindness (Geneva, November 6-10, 1972; WHO Technical Report Series 518), and of the International Council of Ophthalmology [genedx.com]

Deficiency of this enzyme prevents degradation of peptides, thereby leading to accumulation of certain proteins and other compounds in the lysosome. [invitae.com]