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

objectiveTo 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.

methodsData 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.

resultsWe 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.

conclusionsPheWAS 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.