Description

Neuronal ceroid lipofuscinosis (NCL) are a group of hereditary progressive neurodegenerative diseases, characterized by cognitive decline and other neurological functions, epilepsy and vision loss from retinal degeneration, with intracellular accumulation of autofluorescent material, ceroidolipofuscin, in the neuronal cells of the brain and in the retina. The exact incidence and prevalence of this group of diseases is unknown. The clinical presentation of the different forms varies enormously, but the shared characteristic clinical picture is characterized by the association between dementia, vision loss and epilepsy. Symptoms can begin between the neonatal age and young adulthood, depending on the forms, and the original classification of NCL is based on the age of onset, which is divided into forms of congenital, infantile, late infantile NCL, juvenile and adult (see these terms). A variant of Nordic epilepsy (progressive epilepsy – cognitive impairment, Finnish type; see this term) has also been described, in which vision problems can be missing or be mild and not detected. To date, at least 10 forms of NCL have been described, from CLN1 to CLN10. Most NCLs are inherited in an autosomal recessive manner, although an autosomal dominant inheritance form at onset in adulthood has been described as CLN4. The diagnosis is based on the clinical picture, on the accumulation of material with autofluorescent ceroid lipo-pigments on electron microscope analysis, on the deficiency of palmitoyl-protein thioesterase 1, tripeptidyl-peptidase 1 and cathepsin D on enzyme tests, in patients with CLN1, CLN2 and CLN10, respectively. With the exception of CLN4 and CLN9 (for which the disease gene has not yet been identified), the diagnosis can be confirmed with the molecular test. Differential diagnosis includes other diseases associated with vision loss, dementia and epilepsy, with a compatible age of onset (typically mitochondrial diseases, congenital errors of metabolism and other lysosomal storage diseases). Antenatal molecular diagnosis is possible if the causative mutation has already been identified in the family, alternatively enzymatic analysis is possible in some cases. There are no curative therapies for NCLs and the interventions are only symptomatic. Although all NCLs result in severe disability, the prognosis varies and life expectancy is between a few hours or a few days after birth, in the congenital form, up to the fifth decade, in adult patientsNeuronal ceroid lipofuscinosis (NCL) are a group of hereditary progressive neurodegenerative diseases, characterized by cognitive decline and other neurological functions, epilepsy and vision loss from retinal degeneration, with intracellular accumulation of autofluorescent material, ceroidolipofuscin, in the neuronal cells of the brain and in the retina. The exact incidence and prevalence of this group of diseases is unknown. The clinical presentation of the different forms varies enormously, but the shared characteristic clinical picture is characterized by the association between dementia, vision loss and epilepsy. Symptoms can begin between the neonatal age and young adulthood, depending on the forms, and the original classification of NCL is based on the age of onset, which is divided into forms of congenital, infantile, late infantile NCL, juvenile and adult (see these terms). A variant of Nordic epilepsy (progressive epilepsy – cognitive impairment, Finnish type; see this term) has also been described, in which vision problems can be missing or be mild and not detected. To date, at least 10 forms of NCL have been described, from CLN1 to CLN10. Most NCLs are inherited in an autosomal recessive manner, although an autosomal dominant inheritance form at onset in adulthood has been described as CLN4. The diagnosis is based on the clinical picture, on the accumulation of material with autofluorescent ceroid lipo-pigments on electron microscope analysis, on the deficiency of palmitoyl-protein thioesterase 1, tripeptidyl-peptidase 1 and cathepsin D on enzyme tests, in patients with CLN1, CLN2 and CLN10, respectively. With the exception of CLN4 and CLN9 (for which the disease gene has not yet been identified), the diagnosis can be confirmed with the molecular test. Differential diagnosis includes other diseases associated with vision loss, dementia and epilepsy, with a compatible age of onset (typically mitochondrial diseases, congenital errors of metabolism and other lysosomal storage diseases). Antenatal molecular diagnosis is possible if the causative mutation has already been identified in the family, alternatively enzymatic analysis is possible in some cases. There are no curative therapies for NCLs and the interventions are only symptomatic. Although all NCLs result in severe disability, the prognosis varies and life expectancy is between a few hours or a few days after birth, in the congenital form, up to the fifth decade, in adult patients

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