Urea Cycle defects in Argentina. Rare or undiagnosed diseases? Local experience in its diagnosis and characterization
Urea cycle defects (UCD) are inborn errors of ammonia detoxification / arginine synthesis. The severity of the UCD is very variable depending on the specific mutation involved in correlation with the residual enzymatic function. The exact incidence of UCD in Argentina is unknown due to the absence o...
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | Artículo revista |
| Lenguaje: | Español |
| Publicado: |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2019
|
| Materias: | |
| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/25756 |
| Aporte de: |
| id |
I10-R327-article-25756 |
|---|---|
| record_format |
ojs |
| institution |
Universidad Nacional de Córdoba |
| institution_str |
I-10 |
| repository_str |
R-327 |
| container_title_str |
Revista de la Facultad de Ciencias Médicas de Córdoba |
| language |
Español |
| format |
Artículo revista |
| topic |
urea cycle hyperamonemia rare diseases metabolism Ciclo de la urea hiperamonemia enfermedades raras metabolismo |
| spellingShingle |
urea cycle hyperamonemia rare diseases metabolism Ciclo de la urea hiperamonemia enfermedades raras metabolismo Silvera Ruiz , SM Angaroni, CJ Grosso, CL Guelbert, N Becerra, A Peralta , F Dodelson de Kremer, R Laróvere, LE Urea Cycle defects in Argentina. Rare or undiagnosed diseases? Local experience in its diagnosis and characterization |
| topic_facet |
urea cycle hyperamonemia rare diseases metabolism Ciclo de la urea hiperamonemia enfermedades raras metabolismo |
| author |
Silvera Ruiz , SM Angaroni, CJ Grosso, CL Guelbert, N Becerra, A Peralta , F Dodelson de Kremer, R Laróvere, LE |
| author_facet |
Silvera Ruiz , SM Angaroni, CJ Grosso, CL Guelbert, N Becerra, A Peralta , F Dodelson de Kremer, R Laróvere, LE |
| author_sort |
Silvera Ruiz , SM |
| title |
Urea Cycle defects in Argentina. Rare or undiagnosed diseases? Local experience in its diagnosis and characterization |
| title_short |
Urea Cycle defects in Argentina. Rare or undiagnosed diseases? Local experience in its diagnosis and characterization |
| title_full |
Urea Cycle defects in Argentina. Rare or undiagnosed diseases? Local experience in its diagnosis and characterization |
| title_fullStr |
Urea Cycle defects in Argentina. Rare or undiagnosed diseases? Local experience in its diagnosis and characterization |
| title_full_unstemmed |
Urea Cycle defects in Argentina. Rare or undiagnosed diseases? Local experience in its diagnosis and characterization |
| title_sort |
urea cycle defects in argentina. rare or undiagnosed diseases? local experience in its diagnosis and characterization |
| description |
Urea cycle defects (UCD) are inborn errors of ammonia detoxification / arginine synthesis. The severity of the UCD is very variable depending on the specific mutation involved in correlation with the residual enzymatic function. The exact incidence of UCD in Argentina is unknown due to the absence of neonatal screening or national registry. Most patients are detected symptomatically, increasing morbidity / mortality.
The aim is to present the local experience in diagnosis, molecular findings and monitoring of patients with UCD diagnosed at the Hospital de Niños de Córdoba.
According to the inclusion criteria, 600 patients were studied in the period 1998-2019. Biochemical methods included determination of plasma amino acids and urinary orotic acid by HPLC; quantification of plasma ammonia by spectrophotometry. The genetic study consisted of PCR, enzymatic restriction or direct sequencing, SSCP or MLPA.
49 cases of DCU were diagnosed. Ornithine transcarbamylase (OTC) deficiency was the most frequent UCD observed in 26/49 male (hemizygote) and female (symptomatic heterozygous) patients, with OTC gene exclusive mutations. Argininosuccinate synthase (ASS) deficiency was observed in 19 cases, most of them from a delimited population group of CTLN1 with the same mutation. Argininosuccinate lyase (ASL) deficiency was diagnosed in 4 cases that presented frequent "missense" changes worldwide. Patients presented neonatal onset in 53% of cases, observing a critical evolution after a hyperammonemic crisis with a total global mortality of 57% (28/49 cases) and a disability of 28% (6/21) among survivors. The average detection rate in our center is 30% of the expected per year in Argentina.
Most of the patients in our series showed a severe neonatal onset, with high morbi / mortality. The presence of a high prevalence geographic group of a specific mutation in ASS stands out. This work shows our experience in the characterization of the DCU and indicates that these defects are not rare, but that they need tools for their identification, which will lead to improved results through early diagnosis and timely treatment. |
| publisher |
Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología |
| publishDate |
2019 |
| url |
https://revistas.unc.edu.ar/index.php/med/article/view/25756 |
| work_keys_str_mv |
AT silveraruizsm ureacycledefectsinargentinarareorundiagnoseddiseaseslocalexperienceinitsdiagnosisandcharacterization AT angaronicj ureacycledefectsinargentinarareorundiagnoseddiseaseslocalexperienceinitsdiagnosisandcharacterization AT grossocl ureacycledefectsinargentinarareorundiagnoseddiseaseslocalexperienceinitsdiagnosisandcharacterization AT guelbertn ureacycledefectsinargentinarareorundiagnoseddiseaseslocalexperienceinitsdiagnosisandcharacterization AT becerraa ureacycledefectsinargentinarareorundiagnoseddiseaseslocalexperienceinitsdiagnosisandcharacterization AT peraltaf ureacycledefectsinargentinarareorundiagnoseddiseaseslocalexperienceinitsdiagnosisandcharacterization AT dodelsondekremerr ureacycledefectsinargentinarareorundiagnoseddiseaseslocalexperienceinitsdiagnosisandcharacterization AT laroverele ureacycledefectsinargentinarareorundiagnoseddiseaseslocalexperienceinitsdiagnosisandcharacterization AT silveraruizsm defectosdelciclodelaureaenargentinaenfermedadesrarasonodiagnosticadasexperiencialocalensudiagnosticoycaracterizacion AT angaronicj defectosdelciclodelaureaenargentinaenfermedadesrarasonodiagnosticadasexperiencialocalensudiagnosticoycaracterizacion AT grossocl defectosdelciclodelaureaenargentinaenfermedadesrarasonodiagnosticadasexperiencialocalensudiagnosticoycaracterizacion AT guelbertn defectosdelciclodelaureaenargentinaenfermedadesrarasonodiagnosticadasexperiencialocalensudiagnosticoycaracterizacion AT becerraa defectosdelciclodelaureaenargentinaenfermedadesrarasonodiagnosticadasexperiencialocalensudiagnosticoycaracterizacion AT peraltaf defectosdelciclodelaureaenargentinaenfermedadesrarasonodiagnosticadasexperiencialocalensudiagnosticoycaracterizacion AT dodelsondekremerr defectosdelciclodelaureaenargentinaenfermedadesrarasonodiagnosticadasexperiencialocalensudiagnosticoycaracterizacion AT laroverele defectosdelciclodelaureaenargentinaenfermedadesrarasonodiagnosticadasexperiencialocalensudiagnosticoycaracterizacion |
| first_indexed |
2024-09-03T21:00:59Z |
| last_indexed |
2024-09-03T21:00:59Z |
| _version_ |
1809210156314001408 |
| spelling |
I10-R327-article-257562024-08-27T18:26:12Z Urea Cycle defects in Argentina. Rare or undiagnosed diseases? Local experience in its diagnosis and characterization Defectos del Ciclo de la Urea en Argentina. ¿Enfermedades raras o no diagnosticadas? Experiencia local en su diagnóstico y caracterización Silvera Ruiz , SM Angaroni, CJ Grosso, CL Guelbert, N Becerra, A Peralta , F Dodelson de Kremer, R Laróvere, LE urea cycle hyperamonemia rare diseases metabolism Ciclo de la urea hiperamonemia enfermedades raras metabolismo Urea cycle defects (UCD) are inborn errors of ammonia detoxification / arginine synthesis. The severity of the UCD is very variable depending on the specific mutation involved in correlation with the residual enzymatic function. The exact incidence of UCD in Argentina is unknown due to the absence of neonatal screening or national registry. Most patients are detected symptomatically, increasing morbidity / mortality. The aim is to present the local experience in diagnosis, molecular findings and monitoring of patients with UCD diagnosed at the Hospital de Niños de Córdoba. According to the inclusion criteria, 600 patients were studied in the period 1998-2019. Biochemical methods included determination of plasma amino acids and urinary orotic acid by HPLC; quantification of plasma ammonia by spectrophotometry. The genetic study consisted of PCR, enzymatic restriction or direct sequencing, SSCP or MLPA. 49 cases of DCU were diagnosed. Ornithine transcarbamylase (OTC) deficiency was the most frequent UCD observed in 26/49 male (hemizygote) and female (symptomatic heterozygous) patients, with OTC gene exclusive mutations. Argininosuccinate synthase (ASS) deficiency was observed in 19 cases, most of them from a delimited population group of CTLN1 with the same mutation. Argininosuccinate lyase (ASL) deficiency was diagnosed in 4 cases that presented frequent "missense" changes worldwide. Patients presented neonatal onset in 53% of cases, observing a critical evolution after a hyperammonemic crisis with a total global mortality of 57% (28/49 cases) and a disability of 28% (6/21) among survivors. The average detection rate in our center is 30% of the expected per year in Argentina. Most of the patients in our series showed a severe neonatal onset, with high morbi / mortality. The presence of a high prevalence geographic group of a specific mutation in ASS stands out. This work shows our experience in the characterization of the DCU and indicates that these defects are not rare, but that they need tools for their identification, which will lead to improved results through early diagnosis and timely treatment. Los defectos del ciclo de la urea (DCU) son errores innatos de la desintoxicación del amonio/síntesis de arginina. La gravedad de los DCU es muy variable dependiendo de la mutación específica involucrada en correlación con la función enzimática residual. La incidencia exacta de los DCU en Argentina es desconocida debido a la ausencia de pesquisa neonatal o registro nacional. La mayoría de los pacientes se detectan sintomáticamente, aumentando la morbi/mortalidad. El objetivo de este tabajo es presentar una experiencia local en diagnóstico, hallazgos moleculares y monitorización de pacientes con DCU diagnosticados en el Hospital de Niños de Córdoba. Según los criterios de inclusión se estudiaron 600 pacientes, período 1998-2019. Los métodos bioquímicos incluyeron la determinación de aminoácidos plasmáticos y ácido orótico urinario por HPLC; cuantificación del amonio plasmático por espectrofotometría; el estudio genético consistió en PCR, restricción enzimática o secuenciación directa, SSCP o MLPA. Se diagnosticaron 49 casos de DCU. La deficiencia de ornitina transcarbamilasa (OTC) fue el DCU más frecuente observado en 26/49 pacientes varones (hemicigos) y mujeres (heterocigotas sintomáticas), con mutaciones privativas del gen OTC. La deficiencia de argininosuccinato sintasa (ASS) fue observada en 19 casos, la mayoría de ellos de un grupo poblacional delimitado de CTLN1 con igual mutación. La deficiencia de argininosuccinato liasa (ASL) se diagnosticó en 4 casos que presentaban cambios “missense” frecuentes a nivel mundial. El 53% de los pacientes presentó inicio neonatal, observándose una evolución crítica luego de una crisis hiperamonémica con una mortalidad global total de 57% (28/49 casos) y una discapacidad del 28% (6/21) entre los sobrevivientes. La tasa de detección promedio en nuestro centro es el 30% de lo esperado por año en Argentina. La mayoría de los pacientes en nuestra serie mostraron un inicio neonatal severo, con una alta morbi/mortalidad. Se destaca la presencia de un grupo geográfico de alta prevalencia de una mutación puntual en ASS. Este trabajo muestra nuestra experiencia en la caracterización de los DCU y señala que estos defectos no son raros, sino que necesitan herramientas para su identificación, lo que llevará a mejorar los resultados a través del diagnóstico temprano y tratamiento oportuno. Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología 2019-10-15 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion application/pdf https://revistas.unc.edu.ar/index.php/med/article/view/25756 Revista de la Facultad de Ciencias Médicas de Córdoba.; 2019: Suplemento JIC XX Revista de la Facultad de Ciencias Médicas de Córdoba; 2019: Suplemento JIC XX Revista da Faculdade de Ciências Médicas de Córdoba; 2019: Suplemento JIC XX 1853-0605 0014-6722 10.31053/1853.0605.v76.nSuplemento spa https://revistas.unc.edu.ar/index.php/med/article/view/25756/27431 Derechos de autor 2019 Universidad Nacional de Córdoba https://creativecommons.org/licenses/by-nc/4.0 |