Joshua L Bonkowsky1, Jacob Wilkes1, Jian Ying1, Wei-Qi Wei1. 1. Division 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.
Abstract
OBJECTIVE: To determine shared comorbidities and to identify underrecognized or unexpected morbidities in children with leukodystrophies using an unbiased phenome-wide association study (PheWAS) analysis of a nationwide pediatric clinical and financial database. METHODS: Data were extracted from the Pediatric Health Information System database. Patients with leukodystrophy were identified with International Classification of Diseases, 10th revision, clinical modification, diagnostic codes for any of 4 specific leukodystrophies (X-linked adrenoleukodystrophy (E71.52x), Hurler disease (E76.01), Krabbe disease (E75.23), and metachromatic leukodystrophy (E75.25)) over a 3-year time period. Confirmed leukodystrophy cases (n = 553) were matched with 1659 controls. A PheWAS analysis was performed on all available ICD diagnostic codes for cases and controls. Comparisons were performed for all 4 leukodystrophies as a group and individually. RESULTS: We found 174 phecodes (grouped ICD codes) associated with leukodystrophies, including 28 codes with a rate difference (RD) > 20%. Known comorbidities of leukodystrophies including developmental delay, epilepsy, and adrenal insufficiency were identified. Unexpected associations identified included hypertension (RD 30%, OR 25), hearing loss (RD 28%, OR 15), and cardiac dysrhythmias (RD 27%, OR 9). Hurler disease had a greater number of unique disease conditions. CONCLUSIONS: PheWAS analysis from a national database demonstrates shared and unique features of leukodystrophies. Developmental delay, cardiac dysrhythmias, fluid and electrolyte disturbances, and respiratory issues were common to all 4 leukodystrophy diseases. Use of a PheWAS in leukodystrophies and other pediatric neurologic diseases offers a method for targeting improved care for patients by identification of morbidities.
OBJECTIVE: To determine shared comorbidities and to identify underrecognized or unexpected morbidities in children with leukodystrophies using an unbiased phenome-wide association study (PheWAS) analysis of a nationwide pediatric clinical and financial database. METHODS: Data were extracted from the Pediatric Health Information System database. Patients with leukodystrophy were identified with International Classification of Diseases, 10th revision, clinical modification, diagnostic codes for any of 4 specific leukodystrophies (X-linked adrenoleukodystrophy (E71.52x), Hurler disease (E76.01), Krabbe disease (E75.23), and metachromatic leukodystrophy (E75.25)) over a 3-year time period. Confirmed leukodystrophy cases (n = 553) were matched with 1659 controls. A PheWAS analysis was performed on all available ICD diagnostic codes for cases and controls. Comparisons were performed for all 4 leukodystrophies as a group and individually. RESULTS: We found 174 phecodes (grouped ICD codes) associated with leukodystrophies, including 28 codes with a rate difference (RD) > 20%. Known comorbidities of leukodystrophies including developmental delay, epilepsy, and adrenal insufficiency were identified. Unexpected associations identified included hypertension (RD 30%, OR 25), hearing loss (RD 28%, OR 15), and cardiac dysrhythmias (RD 27%, OR 9). Hurler disease had a greater number of unique disease conditions. CONCLUSIONS: PheWAS analysis from a national database demonstrates shared and unique features of leukodystrophies. Developmental delay, cardiac dysrhythmias, fluid and electrolyte disturbances, and respiratory issues were common to all 4 leukodystrophy diseases. Use of a PheWAS in leukodystrophies and other pediatric neurologic diseases offers a method for targeting improved care for patients by identification of morbidities.
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