Raquel Yahyaoui1,2, Javier Blasco-Alonso3, Carmen Benito4, Enrique Rodríguez-García2,5, Fernando Andrade6, Luis Aldámiz-Echevarría6, María C Muñoz-Hernández7, Ana I Vega8, Celia Pérez-Cerdá8, María L García-Martín7, Belén Pérez8. 1. Laboratory of Metabolic Disorders and Newborn Screening Center of Eastern Andalusia, Málaga Regional University Hospital, Málaga, Spain. 2. Grupo Endocrinología y Nutrición, Diabetes y Obesidad, Instituto de Investigación Biomédica de Málaga-IBIMA. 3. Department of Pediatrics, Málaga Regional University Hospital, Málaga, Spain. 4. Department of Genetics, Málaga Regional University Hospital, Málaga, Spain. 5. Laboratorios Vircell, SL, Granada, Spain. 6. Metabolomics Platform, Metabolism Group, BioCruces Health Research Institute, CIBERER, Barakaldo, Spain. 7. BIONAND, Andalusian Center for Nanomedicine and Biotechnology, Junta de Andalucía, Universidad de Málaga, Málaga, Spain. 8. Centro Diagnóstico de Enfermedades Moleculares (CEDEM), Centro de Biología Molecular, Universidad Autónoma de Madrid, CIBERER, idiPAZ, Madrid, Spain.
Abstract
PURPOSE: We report a patient with a human cationic amino acid transporter 2 (CAT-2) defect discovered due to a suspected arginase 1 deficiency observed in newborn screening (NBS). METHODS: A NBS sample was analyzed using tandem mass spectrometry. Screen results were confirmed by plasma and urine amino acid quantification. Molecular diagnosis was done using clinical exome sequencing. Dimethylated arginines were determined by HPLC and nitrate/nitrite levels by a colorimetric assay. The metabolomic profile was analyzed using 1D nuclear magnetic resonance spectroscopy. RESULTS: A Spanish boy of nonconsanguineous parents had high arginine levels in a NBS blood sample. Plasma and urinary cationic amino acids were high. Arginase enzyme activity in erythrocytes was normal and no pathogenic mutations were identified in the ARG1 gene. Massive parallel sequencing detected two loss-of-function mutations in the SLC7A2 gene. Currently, the child receives a protein-controlled diet of 1.2 g/kg/day with protein-and amino-acid free infant formula, 30 g/day, and is asymptomatic. CONCLUSION: We identified a novel defect in human CAT-2 due to biallelic pathogenic variants in the SLC7A2 gene. The characteristic biochemical profile includes high plasma and urine arginine, ornithine, and lysine levels. NBS centers should know of this disorder since it can be detected in arginase 1 deficiency screening.
PURPOSE: We report a patient with a humancationic amino acid transporter 2 (CAT-2) defect discovered due to a suspected arginase 1 deficiency observed in newborn screening (NBS). METHODS: A NBS sample was analyzed using tandem mass spectrometry. Screen results were confirmed by plasma and urine amino acid quantification. Molecular diagnosis was done using clinical exome sequencing. Dimethylated arginines were determined by HPLC and nitrate/nitrite levels by a colorimetric assay. The metabolomic profile was analyzed using 1D nuclear magnetic resonance spectroscopy. RESULTS: A Spanish boy of nonconsanguineous parents had high arginine levels in a NBS blood sample. Plasma and urinary cationic amino acids were high. Arginase enzyme activity in erythrocytes was normal and no pathogenic mutations were identified in the ARG1 gene. Massive parallel sequencing detected two loss-of-function mutations in the SLC7A2 gene. Currently, the child receives a protein-controlled diet of 1.2 g/kg/day with protein-and amino-acid free infant formula, 30 g/day, and is asymptomatic. CONCLUSION: We identified a novel defect in humanCAT-2 due to biallelic pathogenic variants in the SLC7A2 gene. The characteristic biochemical profile includes high plasma and urine arginine, ornithine, and lysine levels. NBS centers should know of this disorder since it can be detected in arginase 1 deficiency screening.