Revised consensus statement on the preventive and symptomatic care of patients with leukodystrophies

Laura A Adang¹, Omar Sherbini², Laura Ball³, Miriam Bloom⁴, Anil Darbari⁵, Hernan Amartino⁶, Donna DiVito², Florian Eichler⁷, Maria Escolar⁸, Sarah H Evans³, Ali Fatemi⁹, Jamie Fraser¹⁰, Leslie Hollowell¹¹, Nicole Jaffe¹², Christopher Joseph⁹, Mary Karpinski¹³, Stephanie Keller¹⁴, Ryan Maddock¹⁵, Edna Mancilla¹⁶, Bruce McClary⁹, Jana Mertz¹⁷, Kiley Morgart¹⁸, Thomas Langan¹⁹, Richard Leventer²⁰, Sumit Parikh²¹, Amy Pizzino², Erin Prange², Deborah L Renaud²², William Rizzo²³, Jay Shapiro⁹, Dean Suhr²⁴, Teryn Suhr²⁴, Davide Tonduti²⁵, Jacque Waggoner²⁶, Amy Waldman¹, Nicole I Wolf²⁷, Ayelet Zerem²⁸, Joshua L Bonkowsky²⁹, Genevieve Bernard³⁰, Keith van Haren³¹, Adeline Vanderver³²; Global Leukodystrophy Initiative (GLIA) Consortium

Affiliations

¹ Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
² Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
³ Center for Translational Science, Children's National Medical Center, Washington, DC, USA; Department of Physical Medicine and Rehabilitation, Children's National Medical Center, Washington, DC, USA.
⁴ Department of Pediatrics, Children's National Medical Center, Washington, DC, USA; Complex Care Program, Children's National Medical Center, Washington, DC, USA.
⁵ Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's National Medical Center, Washington, DC, USA.
⁶ Servicio de Neurología Infantil, Hospital Universitario Austral, Buenos Aires, Argentina.
⁷ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁹ The Hugo W. Moser Research Institute, The Kennedy Krieger Institute, Baltimore, MD, USA.
¹⁰ Rare Disease Institute, Children's National Medical Center, Washington, DC, USA.
¹¹ Complex Care Program, Children's National Medical Center, Washington, DC, USA.
¹² Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹³ Pediatric Multiple Sclerosis Center, Women and Children's Hospital, Buffalo, NY, USA.
¹⁴ Division of Pediatric Neurology, Emory University, Atlanta, GA, USA.
¹⁵ Department of Pediatrics, Children's National Medical Center, Washington, DC, USA.
¹⁶ Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹⁷ Autism Spectrum Disorders Center, Women and Children's Hospital, Buffalo, NY, USA.
¹⁸ Psychiatric Social Work Program, The Kennedy Krieger Institute, Baltimore, MD, USA.
¹⁹ Hunter James Kelly Research Institute, Buffalo, NY, USA.
²⁰ Department of Paediatrics, Murdoch Children's Research Institute, University of Melbourne, Melbourne, Australia.
²¹ Neurogenetics, Neurologic Institute, Cleveland Clinic, Cleveland, OH, USA.
²² Division of Child and Adolescent Neurology, Departments of Neurology and Pediatrics, Mayo Clinic, Rochester, MN, USA.
²³ Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
²⁴ MLD Foundation, West Linn, OR, USA.
²⁵ Department of Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²⁶ Hunter's Hope Foundation, Orchard Park, NY, USA.
²⁷ Department of Child Neurology, VU University Medical Centre and Amsterdam Neuroscience, Amsterdam, The Netherlands.
²⁸ E. Wolfson Medical Center, Tel Aviv, Israel.
²⁹ Department of Pediatrics, Division of Pediatric Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
³⁰ Department of Neurology and Neurosurgery, McGill University, Montreal, Canada; Department of Pediatrics, McGill University, Montreal, Canada; Department of Medical Genetics, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Center, Montreal, Canada.
³¹ Department of Neurology, Lucile Packard Children's Hospital and Stanford University School of Medicine, Stanford, CA, USA.
³² Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Translational Science, Children's National Medical Center, Washington, DC, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: vandervera@email.chop.edu.

PMID: 28863857
PMCID: PMC8018711
DOI: 10.1016/j.ymgme.2017.08.006

Practice Guideline

Revised consensus statement on the preventive and symptomatic care of patients with leukodystrophies

Laura A Adang et al. Mol Genet Metab. 2017 Sep.

. 2017 Sep;122(1-2):18-32.

doi: 10.1016/j.ymgme.2017.08.006. Epub 2017 Aug 20.

Authors

Affiliations

¹ Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
² Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
³ Center for Translational Science, Children's National Medical Center, Washington, DC, USA; Department of Physical Medicine and Rehabilitation, Children's National Medical Center, Washington, DC, USA.
⁴ Department of Pediatrics, Children's National Medical Center, Washington, DC, USA; Complex Care Program, Children's National Medical Center, Washington, DC, USA.
⁵ Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's National Medical Center, Washington, DC, USA.
⁶ Servicio de Neurología Infantil, Hospital Universitario Austral, Buenos Aires, Argentina.
⁷ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁹ The Hugo W. Moser Research Institute, The Kennedy Krieger Institute, Baltimore, MD, USA.
¹⁰ Rare Disease Institute, Children's National Medical Center, Washington, DC, USA.
¹¹ Complex Care Program, Children's National Medical Center, Washington, DC, USA.
¹² Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹³ Pediatric Multiple Sclerosis Center, Women and Children's Hospital, Buffalo, NY, USA.
¹⁴ Division of Pediatric Neurology, Emory University, Atlanta, GA, USA.
¹⁵ Department of Pediatrics, Children's National Medical Center, Washington, DC, USA.
¹⁶ Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
¹⁷ Autism Spectrum Disorders Center, Women and Children's Hospital, Buffalo, NY, USA.
¹⁸ Psychiatric Social Work Program, The Kennedy Krieger Institute, Baltimore, MD, USA.
¹⁹ Hunter James Kelly Research Institute, Buffalo, NY, USA.
²⁰ Department of Paediatrics, Murdoch Children's Research Institute, University of Melbourne, Melbourne, Australia.
²¹ Neurogenetics, Neurologic Institute, Cleveland Clinic, Cleveland, OH, USA.
²² Division of Child and Adolescent Neurology, Departments of Neurology and Pediatrics, Mayo Clinic, Rochester, MN, USA.
²³ Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA.
²⁴ MLD Foundation, West Linn, OR, USA.
²⁵ Department of Child Neurology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
²⁶ Hunter's Hope Foundation, Orchard Park, NY, USA.
²⁷ Department of Child Neurology, VU University Medical Centre and Amsterdam Neuroscience, Amsterdam, The Netherlands.
²⁸ E. Wolfson Medical Center, Tel Aviv, Israel.
²⁹ Department of Pediatrics, Division of Pediatric Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
³⁰ Department of Neurology and Neurosurgery, McGill University, Montreal, Canada; Department of Pediatrics, McGill University, Montreal, Canada; Department of Medical Genetics, Montreal Children's Hospital, McGill University Health Center, Montreal, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Center, Montreal, Canada.
³¹ Department of Neurology, Lucile Packard Children's Hospital and Stanford University School of Medicine, Stanford, CA, USA.
³² Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Translational Science, Children's National Medical Center, Washington, DC, USA; Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. Electronic address: vandervera@email.chop.edu.

PMID: 28863857
PMCID: PMC8018711
DOI: 10.1016/j.ymgme.2017.08.006

Abstract

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.

Keywords: Care; Consensus; Leukodystrophy; Outcomes; Prevention; Therapy.

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Figures

**Fig. 1.**
Examples of orthopedic disorders in children with leukodystrophies. Pelvic tilt in a patient with Krabbe disease is shown by hip radiograph (a). Bilateral coxa valga with bilateral dislocated femoral heads is demonstrated in a patient with Pelizaeus-Merzbacher (b). Severe thoracolumbar scoliosis and pelvic tilt is shown in a patient with X-linked Adrenoleukodystrophy (c).

See this image and copyright information in PMC

References

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Revised consensus statement on the preventive and symptomatic care of patients with leukodystrophies

Affiliations

Revised consensus statement on the preventive and symptomatic care of patients with leukodystrophies

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources