Neuronal Ceroid-Lipofuscinoses type 3 (associated to CLN3)

Neuronal ceroid lipofuscinoses (NCLs) or Batten disease are a group of inherited, neurodegenerative, smooth storage disorders characterized by progressive intellectual and motor impairment, seizures, and premature death. Visual loss is a feature of most forms. The clinical phenotypes are traditionally characterized according to the age of onset and the order of appearance of the clinical features in infantile, late childhood, juvenile, and adult epilepsy.

Pathogenic variants in thirteen genes (PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8, CLN8, CTSD, DNAJC5, CTSF, ATP13A2, GRN, KCTD7) are known to cause NCL. The diagnosis of NCL is based on enzyme activity assay and molecular genetic testing. In unusual cases, diagnosis is based on electron microscopy of biopsied tissues. The diagnostic testing strategy depends on the age of onset.

The diagnostic test strategy depends on the age of onset.

The diagnostic test strategy depends on the age of onset.

NCLs reach the highest incidence values in Northern Europe and the USA with 1 case per 12,500 population.

The incidence of NCLs is highest in Northern Europe and the USA with 1 case per 12,500 population.

In neuronal ceroid lipofuscinosis type 3, symptoms usually appear between 4 and 6 years of age, with rapid vision loss followed by behavioral problems and cognitive impairment. Epilepsy begins around 10 years of age, followed by sleep problems and motor impairment.

The treatments available focus on relieving symptoms. Anticonvulsant drugs are used to prevent or treat seizures. Associated psychiatric and motor disorders can also be controlled when they occur.

In recent years, significant advances have been made toward potential treatments for NCLs such as gene therapy and enzyme replacement therapy. Despite the efforts, only one NCL2-specific drug called Cerliponase alfa (Brineura; Biomarin Pharmaceutical, USA) has been approved in 2017.