Despite these advances in diagnostic efficacy, there are still significant issues with respect to implementation of NGS in clinical settings. Given the unmet diagnostic need amongst patients with persistently unresolved white matter disorders, and the potential for agnostic NGS testing to clarify these cases, the investigators propose a randomized controlled trial (RCT) of 200 leukodystrophy patients at the time of initial confirmation of MRI abnormalities, with prospective collection of patients randomly received on a "first come, first served" basis from a network of expert clinical sites. All participants will undergo WGS in parallel to standard clinical testing in a staggered fashion. The WGS testing will be performed in a clinical services laboratory that is certified under Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathologists (CAP). This approach aims to assess the diagnostic validity and utility of NGS approaches, with primary outcome measures including time to diagnosis and whether or not a diagnosis was achieved.