Leukodystrophies are a group of genetically determined neurodegenerative disorders that predominantly affect the white matter. We aimed to study the clinical, radiological and genetic features of childhood-onset Leukodystrophies by in-house genetic testing using a targeted genetic panel. All children with a clinico-radiological suspicion of leukodystrophy were evaluated by an in-house Ion Torrent next-generation sequencing technology. A custom gene panel was designed with the most common causes of leukodystrophies in the given setting. In the first phase, fourteen children with suspected leukodystrophies were tested by our in-house panel. Of these, 12 (85%) were genetically confirmed. The most common diagnoses were: X-linked adrenoleukodystrophy 25% (n=3), metachromatic leukodystrophy 25% (n=3), and megalencephalic leukoencephalopathy with subcortical cysts 16.6% (n=2). Majority of cases were male 83.3% (n=10). The mean age at presentation was 2.9 years (range birth – 6 years). The common clinical symptoms were global developmental delay 100%, (n=12), gait impairments 58.3%, (n=7), regression in attained milestones 58.3%, (n=7), abnormal body movements 25%, (n=3), seizures 25%, (n=3), poor scholastic performance 25%, (n=3) and speaking difficulty 16.6%, (n=2). Magnetic resonance imaging showed characteristic bilateral symmetrical white matter involvement in all children. We have found 3 novel variants in this study. X- adrenoleukodystrophy and metachromatic leukodystrophy are the common type of leukodystrophies seen in our children. The advent of next generation sequencing has helped in the early genetic confirmation and prenatal counselling for these disorders. Use of in-house targeted genetic panels helps in significant cost reduction and feasibility for the patients in resource-poor settings.