Category: Rare Genetic and Metabolic Diseases
Objective: To delineate clinical, molecular, and radiological landscape of patients with Neurodegeneration with Brain Iron Accumulation (NBIA) in a nationwide Indian cohort.
Background: NBIAs are a complex group of genetic disorders with heterogeneous clinical features. Data from geographically diverse populations remains limited and is crucial in enhanced understanding of key characteristics.
Method: Patients with clinical and/or radiological features consistent with NBIA and genetic confirmation were recruited from 12 centers across India with movement disorders expertise and through Parkinson Research Alliance of India. Participating clinicians completed a predesigned proforma to capture clinical, genetic, and radiological data.
Results: Fifty patients (male: female= 28: 22) with pathogenic variants in six different genes (PLA2G6, PANK2, c9orf12, WDR45, VAC14 and FA2H) were identified. PLA2G6-associated neurodegeneration (PLAN) was the major NBIA subtype (n=25, 52.1%), followed by pantothenate kinase associated neurodegeneration (PKAN) (n=13; 27%), MPAN (n=8; 16.6%) and one each of Wodehouse-Sakati syndrome, FAHN and VAC14-associated neurodegeneration. The outstanding features were dystonia (90%) and parkinsonism (85%) across all NBIAs, with noticeable oromandibular dystonia, retrocollis and opisthotonos. Striking spasticity was seen in MPAN. Patients with PLAN had prominent cognitive impairment (50%), psychiatric abnormalities (25%), pyramidal signs (33.3%), postural instability (40%) cerebellar ataxia (35%), and bowel/bladder disturbances (60%). Iron deposition in basal ganglia/substantia nigra was seen in 85% of PLAN patients. The most common PLA2G6 variant, seen in 45%, was the c.2222G>A variant. All such patients exhibited severe cognitive/psychiatric comorbidities. Two patients with PLAN with levodopa-responsive parkinsonism and early levodopa-induced dyskinesias underwent STN-DBS with good improvement. One patient with atypical PKAN underwent Gpi-DBS and one had pallidotomy with partial benefit.
Conclusion: This study highlights the complex phenotypes observed in patients with NBIA. PLAN was the most common NBIA in Indian patients. Genotype-phenotype correlation was noted for the c.2222G>A variant, which correlated with prominent cognitive and/or psychiatric dysfunction. MRI iron deposition was not seen in 15% patients with PLAN.
To cite this abstract in AMA style:
D. Garg, A. Agarwal, J. Ganguly, R. Kandadai, R. Rajan, S. Kola, D. Radhakrishnan, S. Bhowmick, M. Chandarana, S. Desai, V. Paramanandam, P. Basu, A. Saini, E. Arunmozhimaran, S. Garg, S. Mudassir, L. Sahoo, S. Sharma, H. Kumar, R. Borgohain, A. Garg, P. Kukkle, A. Srivastava. The Landscape of Neurodegeneration with Brain Iron Accumulation in Indian patients: Lessons from a Multicentric Cross-sectional Study [abstract]. Mov Disord. 2024; 39 (suppl 1). https://www.mdsabstracts.org/abstract/the-landscape-of-neurodegeneration-with-brain-iron-accumulation-in-indian-patients-lessons-from-a-multicentric-cross-sectional-study/. Accessed October 7, 2024.« Back to 2024 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-landscape-of-neurodegeneration-with-brain-iron-accumulation-in-indian-patients-lessons-from-a-multicentric-cross-sectional-study/