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Novel and known morbidities of leukodystrophies identified using a phenome-wide association study

Joshua L Bonkowsky1, Jacob Wilkes1, Jian Ying1

  • 1Division of Pediatric Neurology (JLB), Department of Pediatrics, University of Utah School of Medicine; Brain and Spine Center (JLB), Primary Children's Hospital, Intermountain Healthcare, Salt Lake City; Intermountain Healthcare (JW), Salt Lake City; Department of Internal Medicine (JY), University of Utah School of Medicine, Salt Lake City; and Department of Biomedical Informatics (W-QW), Vanderbilt University Medical Center, Nashville, TN.

Neurology. Clinical Practice
|December 10, 2020
PubMed

Insights

A phenome-wide association study (PheWAS) identified shared and unexpected comorbidities in children with leukodystrophies. This analysis helps target improved care by revealing common and unique disease features in pediatric neurologic conditions.

Area of Science:

  • Pediatric Neurology
  • Medical Informatics
  • Genetics

Background:

  • Leukodystrophies are a group of rare genetic disorders affecting the white matter of the brain.
  • Understanding the full spectrum of comorbidities in pediatric leukodystrophies is crucial for comprehensive patient care.
  • Previous studies have focused on known complications, potentially overlooking underrecognized morbidities.

Purpose of the Study:

  • To identify shared and unexpected comorbidities in children diagnosed with four specific leukodystrophies.
  • To utilize a phenome-wide association study (PheWAS) approach for an unbiased assessment of disease associations.
  • To leverage a nationwide pediatric clinical and financial database for robust analysis.

Main Methods:

  • Data were extracted from the Pediatric Health Information System database.
  • Patients with X-linked adrenoleukodystrophy, Hurler disease, Krabbe disease, and metachromatic leukodystrophy were identified using ICD-10 codes.
  • A PheWAS was conducted comparing 553 cases with 1659 controls, analyzing all available diagnostic codes.

Main Results:

  • The analysis identified 174 phecodes associated with leukodystrophies, with 28 showing a rate difference (RD) greater than 20%.
  • Confirmed known comorbidities such as developmental delay, epilepsy, and adrenal insufficiency.
  • Revealed unexpected associations including hypertension (RD 30%), hearing loss (RD 28%), and cardiac dysrhythmias (RD 27%).

Conclusions:

  • PheWAS analysis effectively highlights both shared and unique disease features across different leukodystrophies.
  • Common conditions across the studied leukodystrophies include developmental delay, cardiac dysrhythmias, fluid/electrolyte disturbances, and respiratory issues.
  • Applying PheWAS to pediatric neurologic diseases aids in identifying morbidities to improve patient care strategies.
Abstract

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