Neuronal Ceroid-Lipofuscinoses type 7 (associated to MFSD8)

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.

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

In neuronal ceroid lipofuscinosis type 7, symptoms may appear in infancy, between 2 and 7 years of age. Affected children present with severe neurological symptoms, such as progressive neurodevelopmental disorders and microcephaly, visual impairment, ataxia, speech disturbances and frequent seizures.

The patterns of lipofuscin acómules most frequently observed microscopically in neuronal ceroid lipofuscinosis type 7 comprise mixed combinations of granular, curvilinear, dactyl, and straight profiles.

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.