Know Your Disease: Late Infantile Neuronal Ceroid Lipofuscinosis(LINCL)
What is Late Infantile Neuronal Ceroid Lipofuscinosis?
Discovered in 1998, late infantile neuronal ceroid lipofuscinosis (LINCL) or the Jansky- Bielschowsky disease manifests in a previously healthy child around the 3 rd year of life. A deficiency of tripeptidyl-peptidase 1 (TPP1) results in abnormal storage of proteins and lipids in neurons and other cells. The cells cannot function as they should and symptoms develop. Originally, NCLs are defined by their age of onset and clinical symptoms.
The prevalence of LINCL is unknown. All forms of NCL affect around 1 in 100,000
individuals worldwide. NCLs are more common in Finland, where approximately 1 in
12,500 individuals are affected.
Genetics and risk:?
Classical late infantile NCL (NCL2) is caused by mutations in the CLN2 gene leading
to deficiency of TPP1. Since LINCL is an autosomal recessive disorder, the child
needs to receive the abnormal gene from both parents in order to show any clinical
symptoms. - If an individual receives one normal gene and one gene for the disease,
the person will only be a carrier for the disease - The risk for both carrier parents
to pass the defective gene and have an affected child is 25% with each pregnancy
- The risk to have a child who is a carrier like the parents is 50% with each pregnancy
- The chance for a child to receive normal genes from both parents and be completely
normal is 25% The risk is the same for males and females
Signs and symptoms:?
The signs and symptoms of this condition typically begin in late infancy or early
childhood. The initial features usually include recurrent seizures (epilepsy) and
difficulty in coordinating movements. Affected children also develop muscle twitches
(myoclonus) and vision impairment. LINCL affects motor skills, such as sitting and
walking, and speech development.
The diagnosis can be made by an enzyme study from leucocytes by TPP1 enzyme and
molecular diagnosis can be made by TPP1 (NCL2) gene study. Prenatal diagnosis can
be carried out at 11 weeks of pregnancy by direct chorionic villi study or at 16
weeks by amniotic fluid cultured cells for the enzyme or molecular study in case
of known identified mutation in the gene.
Current disease management is primarily targeted at controlling the symptoms rather
than "curing" the disease. Seizures can sometimes be reduced or controlled
with anticonvulsant drugs, and other medical problems can be treated appropriately
as they arise.
Early diagnosis of the disease is important for counseling the affected families about future pregnancies through prenatal diagnosis..
Williams RE, Abergb L, Auttic T, Goebeld HH, Kohlschüttere A, Lönnqvistb T. Diagnosis
of the neuronal ceroidlipofuscinoses: An update. Biochim. Biophys. Acta Molecular
Basis of Disease 2006 Oct;1762(10):865-872. 2 What Is Batten Disease?: Batten Disease
Support and Research Foundation. Available online at: http://bdsra.org/what-is- batten-disease/. Last accessed in April 2016. 3 Late Infantile Neuronal CeroidLipofuscinosis:
Genetic Home Reference. Available online at: https://ghr.nlm.nih.gov/condition/late-infantile-
neuronal-ceroid- lipofuscinosis. Last accessed in April 2016.