1. Amino acid Profiling Research Center for Genetic Engineering and Biotechnology “Georgi D. Efremov”, MASA What is amino acid profiling? Amino acids are the basic structural units of the proteins and could be easily detected in any biological fluid. Profiling of amino acids in plasma and urine has been used to elucidate a rapidly growing number of aminoacidopathies. Clinical Background Primary aminoacidopathies are typically autosomal recessive or X-linked inherited disorders resulting from a deficient enzyme or transport protein. Hyperaminoacidemias and hyperaminoacidurias typically indicate genetically inherited metabolic enzyme impairments such as phenylketonuria, tyrosinemia, cystinuria or can detect renal transport disorders. Inherited metabolic disorders generally result in accumulation or the deficiency of one or more amino acids in biological fluids, and the abnormality is easily detected in either specimen type. Symptoms range from relatively benign to severe including growth and mental retardation, developmental delay, learning disabilities, seizures, lethargy, vomiting, metabolic acidosis or alkalosis or osteoporosis. Quantification of amino acids can also be performed on spinal fluid for confirmation of a diagnosis and to assess the degree of brain involvement in metabolic defects of biogenic amine neurotransmitters. Abnormal amino acid patterns can provide key information about physiological and pathological metabolic status in patients. Early diagnosis of metabolic disorders and amino acids impairment should provide early treatment and dietary management. Depending on the natural history of the disorder, early diagnosis would lead to minimization or prevention of clinical symptoms. Analysis performed at RCGEB “ Georgi D. Efremov ” Price (МКД) Amino acid analysis (Biochrom 30)6.000 Literature: 1.P art 8. Amino Acids. In: Scriver CR, Beaudet AL, Valle D, Sly WS, Childs B, Kinzler KW, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill, Inc; 2001;1665-2105. 2.Part IV. Disorders of amino acid metabolism and transport. Fernandes J, Saudubray J-M, Van den Berghe G, eds. Inborn Metabolic Diseases Diagnosis and Treatment. 3 rd ed. New York, NY: Springer; 2000;169-273. 3.Sukarova Stefanovska E., Popovska-Jankovic K., Gucev Z., Tasic V., Jotovska O., Plaseska-Karanfilska D. Quantitative amino acid analysis in rare diseases – our experience. Rare Diseases in South-Eastern Europe; Skopje, Macedonia, November 15-17, 2012 Material for testing  Whole blood specimens collected in sterile tubes with EDTA as anticoagulant;  Urine specimen (Creatinine concentration should be supplied)  Cerebrospinal fluid RCGEB, 2013 Who should be tested: Children suspected for:  inborn metabolic errors,  renal diseases,  children with neurological impairment, (autism, developmental delay or mental retardation) Method Amino acid analysis in biological fluids is a routine analysis performed in RCGEB “Georgi D. Efremov”, for almost 20 years. Quantitative amino acid analysis is performed using ion-exchange chromatography with post- column ninhydrin derivatization method on Biochrom 30 amino acid analyzer. This method remains a gold standard for detection of inborn errors of amino acid catabolism and transport. Common Aminoacidopathies and Associated Amino Acid Elevations Primary AminoacidopathiesElevated Amino Acids Arginase deficiencyArginine, glutamine CitrullinemiaCitrulline, glutamine Cystinuria Cystine, ornithine, lysine, arginine (urine only) HomocystinuriaHomocystine Maple syrup urine disease (MSUD) Valine, isoleucine, leucine, alloisoleucine Phenylketonuria (PKU)Phenylalanine Tyrosinemia Tyrosine Secondary Aminoacidopathies HyperammonemiaGlutamine Lactic acidosisAlanine Organic acidurias, selectedGlycine Transient tyrosinemia of the newborn Tyrosine