Leukodystrophies are a broad class of genetic disorders that result in disruption or destruction of central myelination. Although the mechanisms underlying these disorders are heterogeneous, there are many common symptoms that affect patients irrespective of the genetic diagnosis. The comfort and quality of life of these children is a primary goal that can complement efforts directed at curative therapies. Contained within this report is a systems-based approach to management of complications that result from leukodystrophies. We discuss the initial evaluation, identification of common medical issues, and management options to establish a comprehensive, standardized care approach. We will also address clinical topics relevant to select leukodystrophies, such as gallbladder pathology and adrenal insufficiency. The recommendations within this review rely on existing studies and consensus opinions and underscore the need for future research on evidence-based outcomes to better treat the manifestations of this unique set of genetic disorders.

Thanks to the seminal work of Robert Anda and Vincent Felitti, it is now widely accepted that adverse childhood experiences (ACEs) can have lifelong effects on physical, behavioral, and mental health and that many adult diseases can be considered developmental disorders that began early in life. Genomics has advanced the neurobiological understanding that underpins ACEs, wellness, and disease, which are modulated through stress pathways and epigenetic modifications. While data are currently limited, children with developmental disabilities have an increased ACE risk compared to typically developing peers. This recognition has important ramifications for health and policy interventions that address the root causes of ACEs, especially in this vulnerable population. With increased societal recognition, advances in policy will lead to medical, financial, and public benefits in years to come, hopefully changing healthcare models from ‘sick care’ to ‘well care’. Adverse childhood experience (ACE) research has refocused medicine from the question ‘What is wrong with you?’ to ‘What happened to you?’. Adopting ACE research into public policy can redirect healthcare models from providing ‘sick care’ to promoting ‘well care’. Not exploring the role of ACEs in children with developmental disabilities leads to further vulnerability and morbidity. ACEs can be mitigated by early identification and implementation of evidence‐based interventions.