CLN5 disease

CLN5 disease, also known as neuronal ceroid lipofuscinosis type 5 (CLN5), is a rare inherited lysosomal storage disorder belonging to the group of neuronal ceroid lipofuscinoses (NCLs), sometimes collectively referred to as Batten disease. It was originally described as the Finnish variant of late infantile neuronal ceroid lipofuscinosis. The disease is caused by mutations in the CLN5 gene, which encodes a soluble lysosomal protein involved in lipid metabolism and intracellular trafficking. The deficiency of functional CLN5 protein leads to the accumulation of ceroid lipofuscin, an autofluorescent lipopigment, within lysosomes of neurons and other cells, resulting in progressive neurodegeneration. CLN5 disease primarily affects the central nervous system. Children typically develop normally in early life, with symptom onset usually occurring between ages 4 and 7 years. Key clinical features include progressive motor decline with clumsiness and ataxia, visual impairment progressing to blindness, cognitive decline and loss of previously acquired skills (developmental regression), seizures (including myoclonic and generalized tonic-clonic types), and behavioral changes. As the disease progresses, affected individuals develop severe intellectual disability, loss of speech, spasticity, and eventually become bedridden. Brain MRI typically shows progressive cerebral and cerebellar atrophy. The disease follows a relentlessly progressive course, with life expectancy generally reduced to the second or third decade of life, though variability exists. There is currently no cure for CLN5 disease. Treatment is primarily supportive and symptomatic, focusing on seizure management with antiepileptic medications, physical and occupational therapy to maintain function as long as possible, nutritional support, and palliative care. Gene therapy and enzyme replacement approaches are under investigation in preclinical studies. Genetic counseling is recommended for affected families. The disease is classified under ICD-10 code E75.4 (neuronal ceroid lipofuscinosis).

Common questions about CLN5 disease