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]

• 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

  loss 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 [rarediseases.info.nih.gov]

• Learning Difficulties

  The disease affects brain cells, and leads to blindness, fits (epilepsy), difficulties with movements and learning difficulties. At the moment, there is no cure, and even with current treatments, children usually die by the age of 12 years old. [io.nihr.ac.uk]

• 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]

• 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]

  Most patients had a highly predictable disease course with symptom onset between 2 and 4 years of age and disease progression with complete loss of motor, language, and visual functions by 4–7.5 years of age. [ajnr.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]

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

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

[…] to gain the best results from treatment. [onlinelibrary.wiley.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]

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]

1 Prenatal testing for late infantile neuronal ceroid lipofuscinosis. 54 56 6 10665500 2000 2 The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland. 56 6 Moore SJ...Parfrey PS 18684116 2008 3 CLN2/TPP1 deficiency: the [malacards.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]