There are about 1500 genetic metabolic diseases. A small number of treatable diseases are diagnosed by newborn screening programs, which are continually being developed. However, most diseases can only be diagnosed based on clinical symptoms or metabolic findings. The main biological fluids used are urine, plasma and, in special situations, cerebrospinal fluid. In contrast to commonly used methods such as gas chromatography and high performance liquid chromatography mass spectrometry, ex vivo proton spectroscopy (1H‐NMR) is not yet used in routine clinical practice, although it has been recommended for more than 30 years. Automatic analysis and improved NMR technology have also expanded the applications used for the diagnosis of inborn errors of metabolism. We provide a mini‐overview of typical applications, especially in urine but also in plasma, used to diagnose common but also rare genetic metabolic diseases with 1H‐NMR. The use of computer‐assisted diagnostic suggestions can facilitate interpretation of the profiles. In a proof of principle, to date, 182 reports of 59 different diseases and 500 reports of healthy children are stored. The percentage of correct automatic diagnoses was 74%. Using the same 1H‐NMR profile‐targeted analysis, it is possible to apply an untargeted approach that distinguishes profile differences from healthy individuals. Thus, additional conditions such as lysosomal storage diseases or drug interferences are detectable. Furthermore, because 1H‐NMR is highly reproducible and can detect a variety of different substance categories, the metabolomic approach is suitable for monitoring patient treatment and revealing additional factors such as nutrition and microbiome metabolism. Besides the progress in analytical techniques, a multiomics approach is most effective to combine metabolomics with, for example, whole exome sequencing, to also diagnose patients with nondetectable metabolic abnormalities in biological fluids. In this mini review we also provide our own data to demonstrate the role of NMR in a multiomics platform in the field of inborn errors of metabolism.

Emotions have an important survival function. Vast amounts of research have demonstrated how affect-related changes in physiology promote survival by effecting short and long-term changes in adaptive behavior. However, if emotions truly serve such an inherent function, they should be pervasive across species and be established early in life. Here, using electroencephalographic (EEG) brain activity we sought to characterize core neurophysiological features underlying affective function at the emergence of emotional expression, i.e., at the developmental age when human infants start to show reliable stimulus-elicited emotional states (4-6 months). Using an approach which eschews traditional EEG frequency band delineations (like theta, alpha), we demonstrate that negative emotional states induce a strong right hemispheric increase in the prominence of the resonant frequency (~5-6 Hz) in the infant frontal EEG. Increased rightward asymmetry was strongly correlated with increased heart rate responses to emotionally negative compared to neutral states. We conclude that functional frontal asymmetry is a key component of emotional processing and suggest that the rightward asymmetry in prominence of the resonant frequency during negative emotional states might reflect functional asymmetry in the central representation of anatomically-driven asymmetry in the autonomic nervous system. Our findings indicate that the specific mode hallmarking emotional processing in the frontal cortex is established in parallel with the emergence of stable emotional states very early during development, despite the well-known protracted maturation of frontal cortex. 3 Significance Statement Emotions provide an important survival function and are associated with unique brain states that should theoretically be present early in life. In this paper, we demonstrate in 4-6 month infants (i.e. when infants first reliably express emotions) that negative emotions are linked to increased prominence in the resonant EEG frequency of the right compared to left frontal cortex. The extent of this asymmetry was linked to heart rate reactivity. These results show that emotion induces asymmetric patterns in brain activity at the emergence of emotional expression, possibly laying the foundation for more complex functional asymmetries observed later in life.