Neurodegeneration With Brain Iron Accumulation In Pediatric Population: Clinico-Radiologic and Genetic Features

Objective: To correlate, clinical and magnetic resonance imaging (MRI) characteristics with genetics, of paediatric patients with Neurodegeneration with brain iron accumulation (NBIA). Methods: 12 paediatric patients, with extrapyramidal features, spasticity, seizures and neuropsychiatric abnormalities in varying combinations with MRI evidence of iron deposition were included. Investigations such as serum ceruloplasmin, ferritin, hormonal profile, smear for acanthocytes, fundus/slit lamp examination, neuropsychological assessment, electroencephalogram and nerve conduction study were done according to the clinical presentation. Targeted/clinical exome gene sequencing was done. Results: 7/12 patients were males ,age of onset ranging from 2-12 years (7.94±3.62). 7 were consanguineous born and 3 had a positive family history. First symptom was dystonia in 11 (all limb onset), and spastic-ataxia in 1. Over the course of illness all had dystonia, 3 had parkinsonism, 2 had ataxia and 1 had hand stereotypies. Oculomotor abnormalities (the most common associated feature) included slow saccades (6) and oculomotor apraxia (1). Neuropsychiatric symptoms (4), pyramidal signs (3), optic disc pallor (1), seizures (1) and retinal pigmentary degeneration (1) were observed. Susceptibility weighted images (SWI) showed mineralisation of globus pallidus in all, substantia nigra in 9, combined RN, DN and striatum in 3. Three had classical “eye of the tiger” sign, 2 had bilateral white matter hyperintensities. Mutations were seen in PANK2 (4), PLA2G6 (3), DCAF17 (2), COASY (1), WDR45 (1) and 1 showed mutation in KMT2B. Conclusion: Neuroimaging and ophthalmological evaluation provide important clues to NBIA diagnosis. PANK2-associated neurodegeneration(PKAN) was the commonest NBIA in pediatric population followed by PLA2G6-associated neurodegeration (PLAN).