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Juvenile neuronal ceroid lipofuscinoses (JNCLs) are a genetically heterogeneous group of neuronal ceroid lipofuscinoses (NCLs; see this term) typically characterized by onset at early school age with vision loss due to retinopathy, seizures and the decline of mental and motor capacities. Worldwide prevalence is unknown. NCL disorders are more frequent in Scandinavian countries and the prevalence and annual birth incidence of JNCLs in Sweden have been estimated at around 1/217,000 and 1/45,000, respectively, whereas in Germany the annual at birth incidence is estimated at around 1/143,000. The classic form of JNCLs (cJNCLs, also referred to as Batten disease and Spielmeyer-Vogt disease) typically manifests with deteriorating vision in an otherwise healthy child at about six years of age. Blindness occurs within a few years. Several years after the onset of visual problems, cognitive abilities decline and epilepsy starts. Dementia and motor disturbances worsen progressively. Psychiatric problems (such as aggressive behavior and sleep problems) have also been reported. Rare cases of JNCL have also been described in which eye involvement is not a striking feature. Epilepsy and dementia without visual loss in these patients may be indicative of a form of JNCL known as the Northern epilepsy variant (progressive epilepsy-intellectual deficit, Finnish type; see this term). JNCLs are transmitted in an autosomal recessive manner and mutations in the following genes may result in JNCL with a classic and/or variant phenotype: PPT1 (designated CLN1; 1p32), TPP1 (11p15; designated CLN2), CLN3 (16p12), CLN8 (8p23; responsible for the Northern epilepsy variant) and CTSD (designated CLN10; 11p15.5). In addition, an entity designated as CLN9 disease has also been described with a phenotype identical to that of classic JNCL but for which the disease-causing gene has not yet been identified. Mutations in the CLN3 gene are the most frequent cause of cJNCL and the diagnostic hallmark of patients with CLN3 disease are lymphocytes with large vacuoles detectable by light microscopy of blood smears. Enzymatic testing is available for deficiencies in palmitoyl-protein thioesterase 1, tripeptidyl-peptidase 1 and cathepsin D, present in patients with PPT1, TPP1 and CTSD mutations, respectively. With the exception of CLN9 disease, molecular testing can be used to confirm the diagnosis. During the initial stage of the disease; retinitis pigmentosa (see this term) may be suspected. Later in the disease course; the differential diagnosis may also include other causes of dementia and seizures at school age, including mitochondrial disorders and subacute sclerosing panencephalitis (see this term). Treatment is supportive only and should consist of palliative care with administration of anticonvulsive drugs; as well as educational, psychological, and psychiatric management. The prognosis for JNCL is severe but life expectancy varies with some patients surviving to the fourth decade. |