Progressive cavitating leukoencephalopathy

Progressive cavitating leukoencephalopathy (PCL) is an extremely rare inherited neurological disorder characterized by progressive white matter deterioration (leukoencephalopathy) with the formation of cystic cavities (cavitations) in the brain. The disease primarily affects the central nervous system, with MRI findings showing diffuse white matter abnormalities and progressive cystic degeneration predominantly in the cerebral and cerebellar white matter. PCL has been associated with mutations in genes involved in mitochondrial function, including APOPT1 (also known as C14orf153) and genes encoding mitochondrial respiratory chain complex components such as NDUFS1 and other mitochondrial-related genes. The ICD-10 classification under E75.2 reflects its categorization among sphingolipidoses and other lipid storage disorders, though the primary pathology relates to mitochondrial dysfunction affecting white matter integrity. Clinical features typically include progressive motor deterioration, spasticity, ataxia, cognitive decline, and in some cases seizures. Affected individuals may initially develop normally before experiencing neurological regression. The severity and rate of progression can vary, with some patients presenting in infancy or early childhood with rapid decline, while others may have a more protracted course. Additional features may include dystonia, visual impairment, and difficulty with speech and swallowing as the disease advances. There is currently no cure or disease-specific treatment for progressive cavitating leukoencephalopathy. Management is supportive and symptomatic, focusing on physical therapy, management of spasticity, seizure control with antiepileptic medications, nutritional support, and multidisciplinary rehabilitation. Genetic counseling is recommended for affected families. Research into mitochondrial therapies and potential targeted treatments is ongoing but remains in early stages.

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