Byline: Sadanandavalli. Chandra, Rita. Christopher, Chakravarthula. Ramanujam, Ganaraja. Harikrishna
Context: Several Enzymes carry out chemical reactions for the production of energy and carrying out normal functioning of the organism. Disorders of these functions can result in permanent damage to the child affecting multiple systems. Most metabolic disorders are at least controllable and therefore it is important to recognize them early for ensuring optimum growth and development. This involves proper pattern recognition by the clinician. Aims: In this study we are discussing a rare treatable metabolic disorder namely Hyperargininemia seen by the authors in the last seven years. Settings and Design: Various parameters of confirmed hyperargininemia patients were analysed. Methods and Material: It is a descriptive study where all patients were confirmed cases with red blood cell arginase levels <10. Statistical Analysis used: Descriptive statistical analysis, Mann-whitney test, spearman’s rho. Results: In this study we found consanguinity in 30 % of patients. At least one sibling was affected in 13 % of patients. Females were more in this group though the pattern remains AR. Symptom onset showed variability from less than 1 year to up to 17 years. Commonest clinical feature was cognitive dysfunction, spasticity, seizures, microcephaly and lesser number with extrapyramidal and cerebellar features. Failure to thrive and dysmorphic features were also seen. Conclusion: Hyperargininemia commonly manifests as regression, failure to thrive, spasticity, seizures with or without microcephaly. When the above phenotype is seen, it is mandatory to screen for urea cycle disorders.
Ammonia is the product of deamination reactions of nitrogenous compounds and is highly toxic to tissues. Urea cycle involves conversion of ammonia to urea. These reactions mainly happen in liver and later transported to kidney for excretion. Urea cycle (Krebs-Henseleit cycle) disorders are a group of inborn errors of metabolism involved in hepatic metabolism of nitrogen to urea. Biosynthesis of urea takes place as follows. To produce one molecule of urea, 3ATP are required, that is, 2 (NH[sub]3) + CO[sub]2 + 3ATP = Urea + H[sub]2O + 3ADP. Ornithine is converted to citrulline catalyzed by carbamoyl phosphate synthase, an enzyme present in hepatic mitochondria. Citrulline ornithine translocase causes entry of ornithine to mitochondria and exit of citrulline. Subsequent reactions take place in cytosol. Argininosuccinate synthetase acts on citrulline and aspartate, and generates argininosuccinate. The enzyme argininosuccinase cleaves this to l-arginine and fumarate. Enzyme arginase acts on arginine, and hydrolytically breaks and yields urea and regenerates ornithine that diffuses back to mitochondria., Hyperargininemia is a relatively rare autosomal-recessive disease due to defect in the arginase I enzyme resulting in high plasma arginine and ammonia levels. The urea cycle carries six enzymatic reactions involved in converting nitrogen to urea, and arginase is the last enzyme in the cycle. Most of these disorders become symptomatic in infancy with encephalopathy due to hyperammonemia and hyperglutaminemia. The enzymes...
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