Metabolic studies in genomic era

Introduction: There are about 1450 Inborn Metabolic Disorders listed in the International Classification of Inherited Metabolic Disorders. The outcome in these disorders depends on the early diagnosis and prompt treatment. However, the diagnosis of these disorders is very complex due to the vast diversity in presentation. With advancement of science and technology, the genomic studies have become easily available and less costly. However, the biochemical studies still have a very important part to play in the early diagnosis of these disorders as well as treatment monitoring. Genomic era has opened many doors of opportunity for improved diagnosis, appropriate and rational treatment, and good follow-up. Aims and Objectives: To understand the relevance and usefulness of metabolic or biochemical tests for identification on inborn errors of metabolism in the genomic era. Materials and Methods: Published literature in English was searched on PubMed using the keywords metabolic studies, new-born screening (NBS), biomarkers, metabolomics, and inborn errors of metabolism. We selected 10 such publications to understand the relevance of biochemical or metabolic studies in the current genomic era. Results and Discussion: Since there is no experimental data or statistics involved here, we will discuss the application of metabolic tests or metabolomics in the current era. Conclusion: Biochemical studies are important for NBS or family screening, diagnostic testing, biomarkers, testing for follow-up of treatment, and prognostication purposes and metabolomics. A combined biochemical and genetic testing approach helps in increasing the diagnostic yield, and hence, it is important to examine a patient clinically and then plan investigations to save time and resources

Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing

Abstract Background Urea cycle disorders (UCDs) are inherited metabolic disorders that present with hyperammonemia, and cause significant mortality and morbidity in infants and children. These disorders are not well reported in the Indian population, due to lack of a thorough study of the clinical and molecular profile. Results We present data from two major metabolic centres in India, including 123 cases of various UCDs. The majority of them (72/123, 58%) presented in the neonatal period (before 30 days of age) with 88% on or before day 7 of life (classical presentation), and had a high mortality (64/72, 88%). Citrullinemia type 1 was the most common UCD, observed in 61/123 patients. Ornithine transcarbamylase (OTC) deficiency was the next most common, seen in 24 cases. Argininosuccinic aciduria was diagnosed in 20 cases. Deficiencies of arginase, N-acetylglutamate synthase, carbamoyl phosphate synthetase, citrin, and lysinuric protein intolerance were also observed. Molecular genetic analysis revealed two common ASS1 mutations: c.470G > A (p.Arg157His) and c.1168G > A (p.Gly390Arg) (36 of 55 tested patients). In addition, few recurrent point mutations in ASL gene, and a deletion of the whole OTC gene were also noted. A total of 24 novel mutations were observed in the various genes studied. We observed a poor clinical outcome with an overall all time mortality of 63% (70/110 cases with a known follow-up), and disability in 70% (28/40) among the survivors. Prenatal diagnosis was performed in 30 pregnancies in 25 families, including one pre-implantation genetic diagnosis. Conclusions We report the occurrence of UCDs in India and the spectrum that may be different from the rest of the world. Citrullinemia type 1 was the most common UCD observed in the cohort. Increasing awareness amongst clinicians will improve outcomes through early diagnosis and timely treatment. Genetic diagnosis in the proband will enable prenatal/pre-implantation diagnosis in subsequent pregnancies

Leucine125Valine (Leu125Val) Gene Polymorphism of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) and Myocardial Infarction in Indian Population

Platelet-endothelial cell adhesion molecule-1 (PECAM-1) has role in atherosclerotic plaque development as well as in thrombosis leading to myocardial infarction (MI). Present study was aimed to analyse the association of PECAM-1 Leu125Val gene polymorphism with MI in Indian population. Subjects included healthy individuals as control (N = 116) and MI patients (N = 100) divided into two groups; MI patients at presentation of the acute event (MI-Group-1, N = 46) and patients with recent event of MI stabilized with treatment 4.5 days from their symptoms (MI-Group-2, N = 54). The difference in the distribution of Leu125Val genotype frequencies of controls and patients did not reach statistical significance. However Leu allele frequency (0.57) was more associated with MI patients as compared to control (0.504). sPECAM-1 levels were significantly elevated in patients at acute event of MI (MI-Group-1) by 44.1% (P = 0.009) as compared to controls and by 95.2% (P = 0.001) as compared to stabilized MI patients (MI-Group-2)