neurodegeneration with brain iron accumulation 2A

Neurodegeneration with brain iron accumulation 2A is a condition that predominantly affects the central nervous system, leading to significant neurological impairment. It is caused by changes in the PLA2G6 gene, which plays a key role in cellular membrane maintenance and repair. The condition most often presents in early childhood, and while precise prevalence estimates are not well established, it is understood to be very rare. Overall, the disorder manifests with progressive neurodegenerative features that necessitate a tailored and multidisciplinary approach to care.

The clinical presentation of neurodegeneration with brain iron accumulation 2A is dominated by neurological features. Characteristically, nearly all affected individuals exhibit cerebral atrophy and gliosis, while many demonstrate psychomotor deterioration, cerebellar atrophy, and developmental regression. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, eventually leading to issues such as mental deterioration, abnormal motor signs like spastic tetraparesis and ataxia, and abnormalities in nerve conduction. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the PLA2G6 gene. PLA2G6 encodes an enzyme that is crucial for the regulation of membrane phospholipids, and disruptions in its function are believed to contribute to the abnormal iron accumulation in the brain. Neurodegeneration with brain iron accumulation 2A is inherited in an autosomal recessive pattern, meaning that an affected child has inherited one altered copy of the gene from each parent. Families are encouraged to seek genetic counseling to understand the recurrence risk and implications for family planning.

Currently, management of neurodegeneration with brain iron accumulation 2A focuses on supportive care and symptom management. Although no FDA-approved treatments are linked to this condition, treatment is tailored to the individual and typically involves a multidisciplinary team to optimize quality of life. In addition to addressing active symptoms, long-term care includes regular surveillance to detect complications early, with input from neurologists, physical therapists, and other specialists as needed. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to support families during decision-making.

The course of neurodegeneration with brain iron accumulation 2A tends to follow a lifelong neurodevelopmental pattern characterized by an initial regression, followed by a period of relative stabilization and, in some individuals, later motor decline. Outcomes vary depending on symptom severity, age of diagnosis, and access to specialized care, and severity and symptoms vary widely between individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition as part of ongoing care and support planning.

Clinical trials are underway exploring new treatment approaches for neurodegeneration with brain iron accumulation 2A. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.