1. Urea cycle disorders in Argentine patients: clinical presentation, biochemical and genetic findings
- Author
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José Antonio Arranz, Johannes Häberle, Raquel Dodelson de Kremer, Norberto Guelbert, Fernanda Peralta, Adriana Becerra, Miriam B. Bezard, Laura E. Laróvere, Celia J. Angaroni, Silene M. Silvera-Ruiz, [Silvera-Ruiz SM, Angaroni CJ, Bezard M] Centro de Estudio de las Metabolopatías Congénitas, Hospital de Niños de la Santísima Trinidad, Cátedra de Clínica Pediátrica, Fac. Cs. Médicas, UNC, Ferroviarios, Córdoba, Argentina. [Arranz JA] Unitat de Metabolopaties, Hospital Universitari Vall d'Hebron, Barcelona, Spain. [Häberle J] University Children's Hospital and Children's Research Center, Zurich, Switzerland. [Guelbert N] Sección Enfermedades Metabólicas, Hospital de Niños de la Santísima Trinidad, Córdoba, Argentina, Vall d'Hebron Barcelona Hospital Campus, University of Zurich, and Silvera-Ruiz, Silene M
- Subjects
Male ,0301 basic medicine ,Argininosuccinic Aciduria ,lcsh:Medicine ,030105 genetics & heredity ,Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Amino Acid Metabolism, Inborn Errors::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Urea Cycle Disorders, Inborn [DISEASES] ,0302 clinical medicine ,Gene duplication ,Ornithine transcarbamylase deficiency ,2736 Pharmacology (medical) ,Hyperammonemia ,Missense mutation ,Pharmacology (medical) ,ARGENTINE PATIENTS ,Child ,Urea Cycle Disorders, Inborn ,Genetics (clinical) ,Citrullinemia ,enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::alteraciones congénitas del metabolismo de los aminoácidos::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::trastornos congénitos del ciclo de la urea [ENFERMEDADES] ,Incidence (epidemiology) ,Argininosuccinate lyase deficiency ,General Medicine ,Otras Ciencias Médicas ,3. Good health ,Child, Preschool ,Urea cycle ,Cohort ,técnicas de investigación::métodos epidemiológicos::características de los estudios epidemiológicos::estudios epidemiológicos::estudios de cohortes [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,INHERITED METABOLIC DISORDERS ,Argininosuccinate synthetase deficiency ,purl.org/becyt/ford/3 [https] ,Female ,2716 Genetics (clinical) ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics::Epidemiologic Studies::Cohort Studies [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Argentina ,purl.org/becyt/ford/3.5 [https] ,UREA CYCLE DEFECTS ,610 Medicine & health ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Molecular epidemiology ,business.industry ,Research ,lcsh:R ,Infant, Newborn ,Infant ,Urea cycle defects ,medicine.disease ,Human genetics ,Ornithine Carbamoyltransferase Deficiency Disease ,10036 Medical Clinic ,Mutation ,Metabolisme, Errors congènits del ,Mètode longitudinal ,business ,HYPERAMMONEMIA ,030217 neurology & neurosurgery - Abstract
The incidence, prevalence, and molecular epidemiology of urea cycle disorders (UCDs) in Argentina remain underexplored. The present study is the first to thoroughly assess the clinical and molecular profiles of UCD patients examined at a single reference center in Argentina. Forty-nine UCD cases were collected. About half (26/49, 53%) manifested neonatally with classical presentation and had a high mortality (25/26, 96%). Ornithine transcarbamylase deficiency (OTCD) was the most common UCD (26 patients). Argininosuccinate synthetase deficiency (ASSD) was detected in 19 cases, while argininosuccinate lyase deficiency (ASLD) was diagnosed in 4 cases. Molecular genetic analysis revealed 8 private OTC mutations and two large deletion/duplication events in the OTC gene. Most mutations in the ASS1 and ASL genes were recurrent missense changes, and four alterations were novel. The clinical outcome of our UCD cohort was poor, with an overall mortality of 57% (28/49 cases), and a 28% (6/21) disability rate among the survivors. Most patients in our case series showed severe neonatal onset, with high morbidity/ mortality. We detected in total 19 mutations, most of them recurrent and of high frequency worldwide. Noteworthy, we highlight the presence of a geographic cluster with high prevalence of a point mutation in the ASS1 gene. This study suggests that these disorders may be more frequent than commonly assumed, and stresses the need for increased awareness amongst health professionals and greater availability of diagnostic tools for accurate identification, earlydiagnosis, and timely treatment. Fil: Silvera Ruiz, Silene Maite. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina Fil: Arranz, José A.. Laboratori de Metabolopaties, Hospital Vall Dhebron; España Fil: Häberle, Johannes. University Children's Hospital And Children´s Research; Suiza Fil: Angaroni, Celia Juana. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina Fil: Bezard, Miriam. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina Fil: Guelbert, Norberto Bernardo. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina Fil: Becerra, Adriana Berónica. Hospital de Niños de la Santísima Trinidad, Córdoba; Argentina Fil: Peralta, Maria Fernanda. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina Fil: Laróvere, Laura Elena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
- Published
- 2019