The diagnosis of inborn errors of metabolism in previously undiagnosed adults referred for medical genetics evaluation

Traditionally thought of as a pediatric diagnostic and therapeutic dilemma, the diagnostic rate and spectrum of inborn errors of metabolism (IEM) in the adult population is largely unknown. A retrospective chart review of patients seen by the Michigan Medicine Adult Medical Genetics Clinic for clinical evaluation from 2014 to 2018 was conducted. Patients referred for a primary indication possibly consistent with an IEM were considered. Variables included age at genetic evaluation, symptom onset age, sex, clinical course, organ systems involved, developmental history, family history and prior genetic testing. Of patients evaluated during the study period, 112 were referred for an indication possibly consistent with an IEM and underwent a complete biochemical workup with an IEM diagnostic rate of 9.8% achieved. An additional 9.8% were diagnosed with a non-IEM genetic diagnosis. Management changes were implemented in all IEM diagnoses. Metabolic disorders in the adult population are under-recognized and under-diagnosed. This report demonstrates the need for clinicians to consider these diagnoses in adults and either refer to a genetics clinic or initiate a biochemical workup. As advances in diagnosis, treatment, and life expectancy of patients with IEMs increases, recognizing and diagnosing these conditions can significantly impact care.