Abstract
Inborn errors of metabolism (IEMs) are rare diseases produced by the accumulation of abnormal amounts of metabolites, toxic to the newborn. When not detected on time, they can lead to irreversible physiological and psychological sequels or even demise. Metabolomics has emerged as an efficient and powerful tool for IEM detection in newborns, children, and adults with late onset. In here, we screened urine samples from a large set of neonates (470 individuals) from a homogeneous population (Basque Country), for the identification of congenital metabolic diseases using NMR spectroscopy. Absolute quantification allowed to derive a probability function for up to 66 metabolites that adequately describes their normal concentration ranges in newborns from the Basque Country. The absence of another 84 metabolites, considered abnormal, was routinely verified in the healthy newborn population and confirmed for all but 2 samples, of which one showed toxic concentrations of metabolites associated to ketosis and the other one a high trimethylamine concentration that strongly suggested an episode of trimethylaminuria. Thus, a non-invasive and readily accessible urine sample contains enough information to assess the potential existence of a substantial number (>70) of IEMs in newborns, using a single, automated and standardized 1H- NMR-based analysis.
Highlights
Inborn errors of metabolism (IEMs) are rare diseases produced by the accumulation of abnormal amounts of metabolites, toxic to the newborn
A third newborn presented high levels of trimethylamine (24 mmol/mol creatinine; probability 0.0014) suggesting the IEM Trimethylaminuria (FMO3) since the normal concentrations in newborns, as determined in our 1H NMR study (Fig. 2), are not higher than 6 mmol/mol creat. This finding should be accompanied by elevated concentrations TMAO, currently unavailable within our method. In this contribution we have investigated novel strategies for an early identification of congenital metabolopathies from 1H NMR data from newborn urine samples
Even though IEMs are individually considered as rare disorders, their collective incidence is considerable and represents a serious public health problem
Summary
Inborn errors of metabolism (IEMs) are rare diseases produced by the accumulation of abnormal amounts of metabolites, toxic to the newborn. More than 1000 IEMs have been described so far[1] While each of these disorders may be considered as a rare disease, in total they constitute a significant socio-economic burden with, for instance, an overall incidence of more than 1 in 1.000 affected newborns in Europe. IEMs represent a serious public threat that involves intensive, long, and expensive treatments While some of these diseases may emerge only in later stages, with chronic and progressive symptoms, most of the neonates with IEMs will develop symptoms typically within hours or days after birth. Correspondence and requests for materials should be addressed to O.M.
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