Neuroferritinopathy is a rare, autosomal dominant neurodegenerative disorder caused by mutations in the FTL gene, which encodes the ferritin light chain. It leads to abnormal iron accumulation in the brain, primarily affecting the basal ganglia. This disorder is classified as a type of neurodegeneration with brain iron accumulation (NBIA). It typically manifests in adulthood, with progressive movement disorders and cognitive impairment.

Pathophysiology

Mutations in the FTL gene lead to structurally abnormal ferritin, impairing iron storage and metabolism. This results in iron accumulation, oxidative stress, and neuronal damage, particularly in the basal ganglia. The globus pallidus, putamen, and caudate nucleus show significant iron deposition, leading to neurodegeneration and movement abnormalities. The disorder primarily affects the extrapyramidal motor system, causing dystonia, chorea, and parkinsonism.

Presenting Symptoms

Symptoms usually begin in adulthood (30s-50s) and progressively worsen. Key clinical features include:

• Movement disorders: Dystonia, chorea, rigidity, bradykinesia, and tremors.
• Cognitive decline: Memory loss and executive dysfunction in later stages.
• Psychiatric symptoms: Depression, anxiety, personality changes.
• Speech and swallowing difficulties: Dysarthria and dysphagia.
• Muscle weakness and atrophy: Leading to motor disability.

Investigations

• MRI brain: Shows iron accumulation in the basal ganglia, with characteristic hypointensities on T2-weighted imaging.
• Genetic testing: Confirms FTL gene mutations.
• Serum ferritin levels: May be normal or slightly low, despite iron overload in the brain.
• Electromyography (EMG): Can be used to assess muscle involvement.

Management

There is no cure for neuroferritinopathy, and treatment is symptomatic:

• Pharmacological:
  • Dopaminergic agents (limited benefit for parkinsonism).
  • Baclofen or botulinum toxin for dystonia.
  • Antidepressants and anxiolytics for psychiatric symptoms.
• Physical therapy: Helps maintain mobility and reduce contractures.
• Speech and occupational therapy: Supports communication and daily activities.