Neuroferritinopathy is a rare autosomal dominant neurodegenerative disorder. It is associated with abnormal iron accumulation in the brain, leading to progressive movement and cognitive impairments.

🧬 Aetiology

Neuroferritinopathy is caused by mutations in the ferritin light chain gene (FTL1) , which plays a critical role in iron storage and regulation.
The most common mutation associated with this condition is the 460InsA mutation in the FTL1 gene, leading to dysfunctional ferritin and abnormal iron metabolism in the brain.

🩺 Clinical Features

Progressive movement disorder: Patients commonly present with chorea, a hyperkinetic movement disorder characterized by involuntary, rapid, and irregular movements.
Focal onset dystonia: This includes blepharospasm (involuntary eyelid closure) and writer’s cramp, along with other forms of dystonia affecting isolated muscles or muscle groups.
Parkinsonism: Some patients may exhibit parkinsonian features such as bradykinesia, rigidity, and tremor.
Action-specific facial dystonia: Facial dystonia, particularly during specific activities like speaking or eating, is a characteristic feature.
Dysphonia: Difficulty speaking or vocal issues are commonly observed as the disease progresses.
Progressive cognitive impairment: Over time, patients develop cognitive decline, memory loss, and other signs of dementia.

Differential Diagnoses

Idiopathic Torsion Dystonia: A condition marked by isolated dystonia without neurodegeneration.
Idiopathic Parkinson’s Disease: Characterized by parkinsonism, but without iron accumulation in the brain.
Huntington’s Disease: A hereditary neurodegenerative disorder associated with chorea and cognitive decline.
Spinocerebellar Ataxia (SCA), particularly SCA17: Genetic neurodegenerative disorders affecting coordination and movement.

🔎 Investigations

Serum Ferritin Levels: Screening for low ferritin levels can be useful in diagnosing neuroferritinopathy, although levels may be within normal limits in pre-menopausal females.
MRI Brain (Gradient Echo): MRI scans often reveal abnormal brain iron accumulation, particularly in the basal ganglia. This finding is seen in all affected individuals.
CSF Analysis: Cerebrospinal fluid (CSF) analysis is typically normal in affected individuals.
CSF Lactate Levels: Normal lactate levels help exclude mitochondrial disorders in the differential diagnosis.

💊 Management

Chorea Management: Tetrabenazine (maximum dose 125 mg) and Sulpiride (400 mg daily) can be used to control chorea symptoms.
Iron Reduction Attempts: Approaches such as venesection (phlebotomy) and desferrioxamine (iron chelation therapy) have not shown proven short-term benefits. Long-term effects are unknown.
Supportive Care: Multidisciplinary management involving neurologists, physiotherapists, and speech therapists can help manage symptoms and maintain quality of life.

References

Brain (2007), 130, 110-119

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Neuroferrinopathy

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