The burden of inherited leukodystrophies in children.
Joshua L. Bonkowsky,Clint Nelson,J. L. Kingston,Francis Filloux,Michael B. Mundorff,Rajendu Srivastava +5 more
TLDR
Overall population incidence is higher than generally appreciated (1 in 7,663 live births), and most leukodystrophies remain undiagnosed, but a logical algorithm based on prevalence could aid testing.Abstract:
Objectives: Leukodystrophies are diseases of the white matter for which data concerning clinical characteristics, incidence, disease burden, and description of outcomes are sparse. The purpose of our study was to determine the incidence and most common types of inherited leukodystrophies in a population, the mortality and time course of deaths, common neurologic features in patients, and health care costs associated with leukodystrophies. Methods: We conducted a retrospective, hospital- and clinic-based surveillance of inherited leukodystrophies among children younger than 18 years presenting to a regional children9s hospital. We enrolled children evaluated from January 1, 1999, through December 31, 2007; clinical information was obtained from medical records. We calculated incidence based on state birth rates. Results: A total of 122 children with an inherited leukodystrophy were identified; 542 patients were excluded. A total of 49% had epilepsy, 43% required a gastrostomy tube, and 32% had a history of developmental regression. Mortality was 34%; average age at death was 8.2 years. No final diagnosis was reported in 51% of patients. The most common diagnoses were metachromatic leukodystrophy (8.2%), Pelizaeus-Merzbacher disease (7.4%), mitochondrial diseases (4.9%), and adrenoleukodystrophy (4.1%). Endocrine abnormalities and hypoplastic cerebellum were noted in significant portions of patients (15% and 14%). Average yearly per-patient medical costs were $22,579. Population incidence was 1 in 7,663 live births. Conclusions: Inherited leukodystrophies are associated with substantial morbidity and mortality in children. Overall population incidence is higher than generally appreciated (1 in 7,663 live births). Most leukodystrophies remain undiagnosed, but a logical algorithm based on prevalence could aid testing.read more
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Journal ArticleDOI
Case Definition and Classification of Leukodystrophies and Leukoencephalopathies
Adeline Vanderver,Morgan Prust,Davide Tonduti,Fanny Mochel,Heather M. Hussey,Guy Helman,James Y. Garbern,Florian Eichler,Pierre Labauge,Patrick Aubourg,Diana Rodriguez,Marc C. Patterson,Johan L.K. Van Hove,Johanna L. Schmidt,Nicole I. Wolf,Odile Boespflug-Tanguy,Raphael Schiffmann,Marjo S. van der Knaap +17 more
TL;DR: A case definition of leukodystrophies and classification of heritable white matter disorders will permit more detailed epidemiologic studies of these disorders and help to study the epidemiology and relevance of geneticwhite matter disorders to public health.
Journal ArticleDOI
A clinical approach to the diagnosis of patients with leukodystrophies and genetic leukoencephelopathies
Sumit Parikh,Geneviève Bernard,Richard J. Leventer,Marjo S. van der Knaap,Johan L.K. Van Hove,Amy Pizzino,Nathan McNeill,Guy Helman,Cas Simons,Johanna L. Schmidt,William B. Rizzo,Marc C. Patterson,Ryan J. Taft,Ryan J. Taft,Ryan J. Taft,Adeline Vanderver,Adeline Vanderver +16 more
TL;DR: A workflow detailing the Global Leukodystrophy Initiative (GLIA) consensus recommendations for an approach to clinical diagnosis is presented, including salient clinical features suggesting a specific diagnosis, neuroimaging features and molecular genetic testing.
Journal ArticleDOI
Global birth prevalence and mortality from inborn errors of metabolism: a systematic analysis of the evidence
TL;DR: The data highlight the need for policy focus on enhanced laboratory capacity for screening and diagnosis, community interventions to tackle parental consanguinity, and increased awareness and knowledge regarding management of IEM, particularly in LMICs.
Journal ArticleDOI
Janus Kinase Inhibition in the Aicardi–Goutières Syndrome
Adeline Vanderver,Laura Adang,Francesco Gavazzi,Katherine McDonald,Guy Helman,David B. Frank,Nicole Jaffe,Sabrina W. Yum,Abigail Collins,Stephanie Keller,Pierre Lebon,Jean-François Meritet,Jullie Rhee,Asako Takanohashi,Thais Armangue,Nicole Ulrick,Omar Sherbini,Jamie Koh,Kyle Peer,Constance Besnier,Carly Scher,Katherine L. Boyle,Holly Dubbs,Julia Kramer-Golinkoff,Amy Pizzino,Sarah Woidill,Justine Shults +26 more
TL;DR: Patients with the Aicardi–Goutieres syndrome, an autosomal recessive disorder that affects the central nervous system, immune system, and skin, have a high level of JAK inhibition.
Journal ArticleDOI
Update on Leukodystrophies: A Historical Perspective and Adapted Definition.
Sietske H. Kevelam,Marjan E. Steenweg,Siddharth Srivastava,Guy Helman,Sakkubai Naidu,Raphael Schiffmann,Susan Blaser,Adeline Vanderver,Nicole I. Wolf,Marjo S. van der Knaap +9 more
TL;DR: A retrospective study concerning three historical cohorts of unclassified leukodystrophy patients is performed and found that currently at least 80% of the patients can be molecularly classified.
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