Urinomics is the study of proteins and metabolites in urine samples. Abnormal urine proteome profile has been detected in many diseases including IEM.

Obtaining a urine sample from a child or neonate is much easier and it is also non-invasive. Hence, diagnosis and management of IEM is going to be much easier with further developments in urinomics. The coming years shall witness more research and developments in this exciting area. The knowledge of proteomic techniques has led to the identification of a variety of urinary markers for the detection of renal Fanconi syndromes [77]. Urinaiy proteomics can be employed for the early diagnosis of Fabry disease [78]. Urinaiy proteomic analysis by MALDI-TOF/MS of Anderson-Fabry disease showed significant increase in alpha-1-antitrypsin, alpha-1-microglobulin, prostaglandin H2 d-isomerase, complement-clq tumor necrosis factor- related protein, and Ig kappa chain V-III [79]. Caubet et al. have reviewed the potential clinically useful urinary biomarkers in ureteropelvic junction (UPJ) obstruction and renal Fanconi syndrome in pediatric population [80].

Unprocessed oligosaccharides and glycoconjugates were detected in urine in patients with glycoproteinosis, Pompe’s disease and sialic acid storage diseases by MALDI-TOF-MS [81]. Urinaiy analysis of free oligosaccharides by MALDTTOF/TOF aids the diagnosis of lysosomal storage disorders [82]. Using label-free quantitative proteomics, two potential markers, prosaposin, and GM2 activator protein (GM2AP), were identified in urine of pediatric patients for pre-symptomatic kidney disease in Type I diabetes and Fabiy disease [83]. An LC-MS/MS method for the simultaneous determination of homovanillic acid, VMA, orotic acid and homogentisic acid in urine has been developed [84]. Acylglycines are important metabolites for the diagnosis of a number of IEM. AUPLC/MS method was developed for the assay of acylglycines in urine samples [85]. Urinaiy steroids were analyzed in patients with 21 hydroxylase deficiency by GC-MS/MS. Many novel steroids some of which may be used as biomarkers were identified [86]. Large number of putative IEM markers was identified in urine by ESI-MS/MS technique by Rebollido-Fernandez et al. [87]. An analytical method for the detection of pterins in urine for the identification of both typical and atypical PKU has been described [88].

Metabolomics is more important in the diagnosis of IEM compared to other branches of clinical medicine, since a large number of small metabolites are excreted in IEM [89]. Urinaiy metabolomics is a useful tool for various disorders neonatal and infancy including IEM [90]. Selicharova et al. usedproteomicsand metabolomics analyses of human hepatocytes in primary cell culture. This technique helped to search the spectrum of proteins and associated metabolites which are affected by the interruption of methyl groupmetabolism. They studied the effect of hyperhomocysteinemia at two concentrations, 0.1 mM and 2.0 mM, and used the inhibitor, BHMT, Betaine Homocysteine N Methyltransferase. The higher concentration produced up-regulation of phosphatidylethanolamine carboxykinase and ornithine aminotransferase, cellular proliferation was affected, secretome composition was altered and signs of apoptosis were seen. In addition, fibrinogen gamma dimers were detected and defective maturation of apolipoprotein A1 was seen [91].


We have reported on the prevalence pattern of inborn errors of metabolism earlier [92-99]. Our studies have found that organic acidurias may be the frequent and common IEM in India. Further studies are needed to find out the actual incidence of various IEM in India. Also, proteomic studies are needed for development of novel markers. TMS teclmique for NBS as practiced in Western countries in not a routine procedure in India.


There are several challenges limiting the use of TMS in clinical situations for NBS. These include cost of the instrument, teclmical expertise, space requirement, etc. There is need for large-scale data interpretation software and teclmical know-how for the use of the same. Also, the laboratories conducting NBS should have policies and procedures for post-analytical systems assessment. These should be addressing, among other things, procedures for immediate reporting of results that are considered out of range or are indicative of a clinical emergency; procedures for obtaining a second, freshly collected specimen for confirmatory analysis for each abnormal screening result, etc.


Historically, analysis for inborn errors of metabolism has been provided predominantly by research laboratories, each offering analyses only for disorders in line with their scientific interest. With the increasing attentiveness of genetics in medicine and nearly one thousand IEMs identified so far, Clinical Biochemical Genetics is now recognized as a laboratory discipline concerned with the estimation and diagnosis of patients and their families with inherited metabolic disease. Further, this discipline helps in monitoring of treatment and also differentiating heterozygous carriers from non-carriers by series of metabolite and enzymatic analysis. Proteomics is definitely the future of medical diagnosis. Developments in this field are occurring rapidly. Specifically in the field of IEM diagnosis and treatment, proteomics is going to play a dynamic role in future. Currently, TMS is widely used in all developed countries and many developing countries for NBS for IEM.

In this commentary, we have highlighted the role of proteomics in detecting novel markers for IEM. Future attempts should be focused on validating these markers so as develop them into tools for early diagnosis of IEM. When used together with TMS, these markers shall aid in the early recognition of IEM. The ultimate aim of many of these research works is to improve both morbidity and mortality for patients with IEM. It is hoped that many of these markers shall satisfy these requirements. Right now, we have a technology which can change the way we look at disease states. It needs to be revealed, whether the technology can deliver the promises it offers, specifically for IEM. Theoretically, it may be possible to identify new markers for IEM by MS; however, they need to undergo the demanding process of validation before being available as useful markers for the detec- tion/diagnosis of IEM. Such markers also need to be clinically useful, cheap, and relevant if it has to be included into the NBS panel. Much work needs to be done in this direction.


• inborn error of metabolism • mass spectrometry • metabolomics • newborn screening • novel markers • proteomics second tier testing • tandem mass spectrometry • urinomics

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