Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease
Introduction: Type III glycogen storage disease (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. The disease is characterized by fasting hypoglycemia, hepatomegaly and progressive myopathy. Molecular analyses of AG...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Instituto Nacional de Salud
2018-05-01
|
| Series: | Biomédica: revista del Instituto Nacional de Salud |
| Subjects: | |
| Online Access: | https://www.revistabiomedica.org/index.php/biomedica/article/view/3454 |
| _version_ | 1818175797592064000 |
|---|---|
| author | Carolina Mantilla Mónica Toro María Elsy Sepúlveda Margarita Insuasty Diana di Filippo Juan Álvaro López Carolina Baquero María Cristina Navas Andrés Augusto Arias |
| author_facet | Carolina Mantilla Mónica Toro María Elsy Sepúlveda Margarita Insuasty Diana di Filippo Juan Álvaro López Carolina Baquero María Cristina Navas Andrés Augusto Arias |
| author_sort | Carolina Mantilla |
| collection | DOAJ |
| description | Introduction: Type III glycogen storage disease (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. The disease is characterized by fasting hypoglycemia, hepatomegaly and progressive myopathy. Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. The full spectrum of AGL mutations in Colombia remains unclear.
Objective: To describe the clinical and molecular characteristics of ten Colombian patients diagnosed with GSD III.
Materials and methods: We recruited ten Colombian children with a clinical and biochemical diagnosis of GSD III to undergo genetic testing. The full coding exons and the relevant exon-intron boundaries of the AGL underwent Sanger sequencing to identify mutation.
Results: All patients had the classic phenotype of the GSD III. Genetic analysis revealed a mutation p.Arg910X in two patients. One patient had the mutation p.Glu1072AspfsX36, and one case showed a compound heterozygosity with p.Arg910X and p.Glu1072AspfsX36 mutations. We also detected the deletion of AGL gene 3, 4, 5, and 6 exons in three patients. The in silico studies predicted that these defects are pathogenic. No mutations were detected in the amplified regions in three patients.
Conclusion: We found mutations and deletions that explain the clinical phenotype of GSD III patients. This is the first report with a description of the clinical phenotype and the spectrum of AGL mutations in Colombian patients. This is important to provide appropriate prognosis and genetic counseling to the patient and their relatives. |
| first_indexed | 2024-12-11T20:06:00Z |
| format | Article |
| id | doaj.art-86cf748545b342ea8c311d1bb7948d65 |
| institution | Directory Open Access Journal |
| issn | 0120-4157 0120-4157 |
| language | English |
| last_indexed | 2024-12-11T20:06:00Z |
| publishDate | 2018-05-01 |
| publisher | Instituto Nacional de Salud |
| record_format | Article |
| series | Biomédica: revista del Instituto Nacional de Salud |
| spelling | doaj.art-86cf748545b342ea8c311d1bb7948d652022-12-22T00:52:24ZengInstituto Nacional de SaludBiomédica: revista del Instituto Nacional de Salud0120-41570120-41572018-05-01380304210.7705/biomedica.v38i0.34542050Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage diseaseCarolina Mantilla0Mónica Toro1María Elsy Sepúlveda2Margarita Insuasty3Diana di Filippo4Juan Álvaro López5Carolina Baquero6María Cristina Navas7Andrés Augusto Arias8Grupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia Hospital Pablo Tobón Uribe, Medellín, ColombiaGrupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo de Inmunodeficiencias Primarias, Universidad de Antioquia, Medellín, Colombia Escuela de Microbiología, Universidad de Antioquia, Medellín, ColombiaHospital Pablo Tobón Uribe, Medellín, ColombiaGrupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, ColombiaGrupo de Gastrohepatología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia Grupo de Inmunodeficiencias Primarias, Universidad de Antioquia, Medellín, Colombia Escuela de Microbiología, Universidad de Antioquia, Medellín, ColombiaIntroduction: Type III glycogen storage disease (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. The disease is characterized by fasting hypoglycemia, hepatomegaly and progressive myopathy. Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. The full spectrum of AGL mutations in Colombia remains unclear. Objective: To describe the clinical and molecular characteristics of ten Colombian patients diagnosed with GSD III. Materials and methods: We recruited ten Colombian children with a clinical and biochemical diagnosis of GSD III to undergo genetic testing. The full coding exons and the relevant exon-intron boundaries of the AGL underwent Sanger sequencing to identify mutation. Results: All patients had the classic phenotype of the GSD III. Genetic analysis revealed a mutation p.Arg910X in two patients. One patient had the mutation p.Glu1072AspfsX36, and one case showed a compound heterozygosity with p.Arg910X and p.Glu1072AspfsX36 mutations. We also detected the deletion of AGL gene 3, 4, 5, and 6 exons in three patients. The in silico studies predicted that these defects are pathogenic. No mutations were detected in the amplified regions in three patients. Conclusion: We found mutations and deletions that explain the clinical phenotype of GSD III patients. This is the first report with a description of the clinical phenotype and the spectrum of AGL mutations in Colombian patients. This is important to provide appropriate prognosis and genetic counseling to the patient and their relatives.https://www.revistabiomedica.org/index.php/biomedica/article/view/3454Glycogen storage disease type III/diagnosisglycogenglycogen debranching enzyme systemglycogenolysis |
| spellingShingle | Carolina Mantilla Mónica Toro María Elsy Sepúlveda Margarita Insuasty Diana di Filippo Juan Álvaro López Carolina Baquero María Cristina Navas Andrés Augusto Arias Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease Biomédica: revista del Instituto Nacional de Salud Glycogen storage disease type III/diagnosis glycogen glycogen debranching enzyme system glycogenolysis |
| title | Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease |
| title_full | Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease |
| title_fullStr | Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease |
| title_full_unstemmed | Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease |
| title_short | Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease |
| title_sort | molecular and clinical characterization of colombian patients suffering from type iii glycogen storage disease |
| topic | Glycogen storage disease type III/diagnosis glycogen glycogen debranching enzyme system glycogenolysis |
| url | https://www.revistabiomedica.org/index.php/biomedica/article/view/3454 |
| work_keys_str_mv | AT carolinamantilla molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease AT monicatoro molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease AT mariaelsysepulveda molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease AT margaritainsuasty molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease AT dianadifilippo molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease AT juanalvarolopez molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease AT carolinabaquero molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease AT mariacristinanavas molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease AT andresaugustoarias molecularandclinicalcharacterizationofcolombianpatientssufferingfromtypeiiiglycogenstoragedisease |