Discussion

Inborn errors of metabolism (IEMs) are inherited metabolic disorders. Most IEMs are caused by defects in the enzymes that help process nutrients, which result in an accumulation of toxic substances or a deficiency of substances needed for normal body function. Making a swift, accurate diagnosis of an IEM is critical in preventing brain damage, organ damage and even death. While there are several hundred recognized IEMs, state public health programs only screen for 40 disorders or fewer at birth, according to NIH. Currently, in order to accurately diagnose if and which IEM is present requires running an array of different targeted assays, which adds to costs and can ultimately only diagnose a limited number of IEMs.

Metabolomic profiling gives us an astonishingly rich view of a patient’s metabolic disturbances through a single test, suggesting that this technology has the potential to be an efficient, first-line phenotyping tool for the diagnosis and monitoring of IEMs, as well as other metabolic diseases. As proof of concept, a discovery set of 200 pediatric plasma samples were tested. The cohort included 130 samples from patients with 21 known IEMs and 70 samples from healthy individuals. The methodology correctly identified 20 of the 21 disorders in the panel that could be screened in plasma. In the clinic, many different biochemical tests would have been required to achieve a similar outcome. Importantly, this methodology accurately identified the affected individual patients when compared to a healthy population, demonstrating the power of this methodology for personalized medicine. Results of this discovery study demonstrate that metabolomic profiling has the potential to detect a wide range of IEMs and could represent an attractive initial screening option for other diseases with a suspected biochemical, genetic origin.