CLN4 disease

CLN4 disease, also known as Kufs disease type B or Parry disease, is a rare form of neuronal ceroid lipofuscinosis (NCL) — a group of inherited neurodegenerative lysosomal storage disorders. CLN4 disease is caused by mutations in the DNAJC5 gene (also known as CSPα, cysteine string protein alpha), which encodes a protein involved in synaptic vesicle function. Unlike most other forms of NCL, CLN4 disease follows an autosomal dominant inheritance pattern and typically presents in adulthood. The disease is characterized by the abnormal accumulation of lipopigments (ceroid and lipofuscin) in neurons and other tissues, leading to progressive neurodegeneration. The primary body system affected is the central nervous system. Key clinical features include progressive myoclonus epilepsy, generalized tonic-clonic seizures, cognitive decline progressing to dementia, cerebellar ataxia, and motor deterioration. Behavioral and psychiatric symptoms may also occur. Notably, unlike childhood-onset forms of NCL, CLN4 disease typically does not cause visual loss or retinal degeneration. Onset usually occurs between the third and fifth decades of life, though variability has been reported. The disease follows a progressive course over years to decades, ultimately leading to severe disability. There is currently no cure or disease-modifying treatment for CLN4 disease. Management is supportive and symptomatic, focusing primarily on seizure control with antiepileptic medications, management of psychiatric symptoms, and multidisciplinary supportive care including physical therapy and occupational therapy. Research into therapies for NCL disorders is ongoing, but specific targeted treatments for CLN4 disease remain unavailable.

Common questions about CLN4 disease