Early Signs and Symptoms of Leukodystrophies: A Case-Based Guide.

1. Maura R.Z. Ruzhnikov, MD*,† 2. Elise Brimble, MS, MSc* 3. Rachel E. Hickey, MS‡ 4. on behalf of the Leukodystrophy Care Network 1. *Department of Neurology and Neurological Sciences and 2. †Division of Medical Genetics, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA. 3. ‡Department of Medical Genetics, Ann & Robert H. Lurie Children's Hospital, Chicago, IL. * Abbreviations: CNS: : central nervous system HSCT: : hematopoietic stem cell transplant MLD: : metachromatic leukodystrophy MRI: : magnetic resonance imaging PMD: : Pelizaeus-Merzbacher disease X-ALD: : X-linked adrenoleukodystrophy 1. Clinicians should be familiar with leukodystrophies as a distinct disease group and with symptoms suggestive of a leukodystrophy requiring prompt evaluation and referral. 2. Clinicians should recognize the urgency of diagnosis for leukodystrophies that have time-sensitive therapies. 3. Clinicians should be knowledgeable about the initial evaluation, recommended referrals, and resources for patients and families with a suspected leukodystrophy. After completing this article, readers should be able to: 1. Recognize symptoms of the more common leukodystrophies, including X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Krabbe disease, and Pelizaeus-Merzbacher disease. 2. Describe the importance and limitations of brain magnetic resonance imaging for recognition and diagnosis of a leukodystrophy. 3. Be aware of the commonly used biochemical and genetic tests when considering a leukodystrophy diagnosis. 4. Formulate a plan for prompt evaluation and referral to appropriate specialists for children with a suspected leukodystrophy. 5. Support families with a diagnosis of a leukodystrophy by providing disease-specific resources. Leukodystrophies are inherited white matter disorders of the central nervous system (CNS) that are often characterized by progressive neurologic decline and early mortality. Early presenting features can be nonspecific and masquerade as common pediatric complaints, including inattention, irritability, or motor delays before progressing to frank developmental regression or neurodegeneration. Without familiarity with these disorders, their early manifestations may seem unrelated before the subsequent decline. The insidious nature of these disorders often leads to a prolonged …