"Practical Approach to Longitudinal Neurologic Care of Adults With X-Li" by Alexandra B. Kornbluh, Aaron Baldwin et al.
 

Practical Approach to Longitudinal Neurologic Care of Adults With X-Linked Adrenoleukodystrophy and Adrenomyeloneuropathy

Alexandra B. Kornbluh, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Aaron Baldwin, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Ali Fatemi, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Adeline Vanderver, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Laura A. Adang, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Keith Van Haren, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Jacinda Sampson, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Florian S. Eichler, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Reza Sadjadi, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Marc Engelen, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.
Jennifer L. Orthmann-Murphy, From the Division of Neurology (A.B.K.), Children's National Hospital, George Washington University Medical School, Washington DC; Division of Neurology (A.B.), Neurogenetics Translational Center of Excellence, University of Pennsylvania, Philadelphia; Kennedy Krieger Institute and The Johns Hopkins University School of Medicine (A.F.), Baltimore, MD; Division of Neurology (A.V., L.A.A.), Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania; Department of Neurology and Pediatrics (K.V.H., J.S.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Palo Alto, CA; Department of Neurology (F.S.E., R.S.), Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatric Neurology (M.E.), Amsterdam UMC location, University of Amsterdam, Amsterdam Leukodystrophy Center, Emma Children's Hospital, Amsterdam Neuroscience, the Netherlands; and Department of Neurology (J.L.O.-M.), University of Pennsylvania, Philadelphia.

Document Type

Journal Article

Publication Date

10-1-2024

Journal

Neurology. Genetics

Volume

10

Issue

5

DOI

10.1212/NXG.0000000000200192

Abstract

Although X-linked adrenoleukodystrophy (ALD) has historically been considered a childhood disease managed by pediatric neurologists, it is one of the most common leukodystrophies diagnosed in adulthood. An increase in both male and female adults reaching diagnosis due to familial cases identified by state newborn screening panels and more widespread use of genetic testing results in a large cohort of presymptomatic or early symptomatic adults. This population is in urgent need of standardized assessments and follow-up care. Adults with ALD/adrenomyeloneuropathy (AMN) may be diagnosed in a variety of ways, including after another family member is identified via genetic testing or newborn screening, presenting for symptomatic evaluation, or following diagnosis with primary adrenal insufficiency. Significant provider, patient, and systems-based barriers prevent adult patients with ALD/AMN from receiving appropriate care, including lack of awareness of the importance of longitudinal neurologic management. Confirmation of and education about the diagnosis should be coordinated in conjunction with a genetic counselor. Routine surveillance for adrenal insufficiency and onset of cerebral ALD (CALD) in men should be performed systematically to avoid preventable morbidity and mortality. While women with ALD do not usually develop cerebral demyelination or adrenal insufficiency, they remain at risk for myeloneuropathy and are no longer considered "carriers." After diagnosis, patients should be connected to the robust support networks, foundations, and research organizations available for ALD/AMN. Core principles of neurologic symptom management parallel those for patients with other etiologies of progressive spastic paraplegia. Appropriate patient candidates for hematopoietic stem cell transplant (HSCT) and other investigational disease-modifying strategies require early identification to achieve optimal outcomes. All patients with ALD/AMN, regardless of sex, age, or symptom severity, benefit from a multidisciplinary approach to longitudinal care spearheaded by the neurologist. This review proposes key strategies for diagnostic confirmation, laboratory and imaging surveillance, approach to symptom management, and guidance for identification of appropriate candidates for HSCT and investigational treatments.

Department

Neurology

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