Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options

• Published in: Biochemical genetics 2018-04, Vol.56 (1-2), p.7-21
• Main Authors: Wasim, Muhammad, Awan, Fazli Rabbi, Khan, Haq Nawaz, Tawab, Abdul, Iqbal, Mazhar, Ayesha, Hina
• Format: Article
• Language: English
• Subjects: Amino acid sequence; Amino acids; Arginase; Argininosuccinic aciduria; Biochemistry; Biomedical and Life Sciences; Biomedicine; Carbamoyl phosphate; Deoxyribonucleic acid; Developing countries; Disorders; DNA; DNA sequencing; Enzymes; Etiology; Genes; Genotyping; High performance liquid chromatography; Homocystinuria; Human Genetics; Hyperammonemia; Inborn errors of metabolism; LDCs; Liquid chromatography; Maple syrup; Maple syrup urine disease; Mass spectrometry; Mass spectroscopy; Medical Microbiology; Medical screening; Metabolic disorders; Metabolic pathways; Metabolism; Methylenetetrahydrofolate reductase; Mutation; Ornithine; Phenylketonuria; Proteins; Pyruvic acid; Review; Syrup; Tetrahydrofolic acid; Urine; Zoology
• ISSN: 0006-2928; 1573-4927
• DOI: 10.1007/s10528-017-9825-6

Inborn errors of metabolism (IEMs) are a group of inherited metabolic disorders which are caused by mutations in the specific genes that lead to impaired proteins or enzymes production. Different metabolic pathways are perturbed due to the deficiency or lack of enzymes. To date, more than 500 IEMs have been reported with most of them being untreatable. However, fortunately 91 such disorders are potentially treatable, if diagnosed at an earlier stage of life. IEMs have been classified into different categories and one class of IEMs, characterized by the physiological disturbances of amino acids is called as aminoacidopathies. Out of 91 treatable IEM, thirteen disorders are amino acid related. Aminoacidopathies can be detected by chromatography and mass spectrometry based analytical techniques (e.g., HPLC, GC–MS, LC–MS/MS) for amino acid level changes, and through genetic assays (e.g., PCR, TaqMan Genotyping, DNA sequencing) at the mutation level in the corresponding genes. Hence, this review is focused to describe thirteen common aminoacidopathies namely: Phenylketonuria (PKU), Maple Syrup Urine Disease (MSUD), Homocystinuria/Methylene Tetrahydrofolate Reductase (MTHFR) deficiency, Tyrosinemia type II, Citrullinemia type I and type II, Argininosuccinic aciduria, Carbamoyl Phosphate Synthetase I (CPS) deficiency, Argininemia (arginase deficiency), Hyperornithinemia–Hyperammonemia–Homocitrullinuria (HHH) syndrome, N -Acetylglutamate Synthase (NAGS) deficiency, Ornithine Transcarbamylase (OTC) deficiency, and Pyruvate Dehydrogenase (PDH) complex deficiency. Furthermore, the etiology, prevalence and commonly used analytical techniques for screening of aminoacidopathies are briefly described. This information would be helpful to researchers and clinicians especially from developing countries to initiate newborn screening programs for aminoacidopathies.