Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomes
Introduction: 11β-hydroxylase (11β-OH) deficiency is the second most frequent cause of classic congenital adrenal hyperplasia (CAH) (5%–8% of cases). Clinically, it is characterized by virilization and arterial hypertension. The objective of this study was to describe the clinical, biochemical and g...
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Elsevier
2025-02-01
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| Series: | Anales de Pediatría (English Edition) |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2341287925000304 |
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| author | Elida Mercado Santis Ariadna Campos Paula Fernández Josep Oriola Diego Yeste Víctor Pérez María Clemente |
| author_facet | Elida Mercado Santis Ariadna Campos Paula Fernández Josep Oriola Diego Yeste Víctor Pérez María Clemente |
| author_sort | Elida Mercado Santis |
| collection | DOAJ |
| description | Introduction: 11β-hydroxylase (11β-OH) deficiency is the second most frequent cause of classic congenital adrenal hyperplasia (CAH) (5%–8% of cases). Clinically, it is characterized by virilization and arterial hypertension. The objective of this study was to describe the clinical, biochemical and genetic characteristics classic 11β-OH deficiency in patients managed in our hospital and its outcomes. Patients and methods: Retrospective longitudinal, observational and descriptive study. Inclusion criteria: Patients with clinical features of virilization, high levels of 11-deoxycortisol and study of CYP11B1 gene with detection of pathogenic and likely pathogenic variants. Results: We identified 6 patients (1 male, 5 female) from 4 families. In the 4 index cases, the median age at diagnosis was 2.3 years. The 46,XX patients exhibited a variable degree of virilization at diagnosis, with a predominance of Prader stage V, and one case of male sex assignment at birth. All patients had elevated serum concentrations of 17-hydroxyprogesterone and testosterone. Fifty percent of the patients had developed arterial hypertension during the follow-up, with onset at a median age of 9.3 years. Three 46,XX patients reached a median final height of 154 cm. Six different variants of theCYP11B1 gene were identified, 5 of which were novel variants (c.595 G > A, c.710 T > C, c.1156delG, c.395 + 2dupT, c.1159dupA). Conclusions: There is considerable heterogeneity in the clinical presentation of patients with CAH due to 11β-OH deficiency. Early diagnosis and treatment are important to prevent complications and improve long-term outcomes. We report 6 different variants of the CYP11B1 gene, including 5 novel variants. Resumen: Introducción: La deficiencia de 11β-hidroxilasa (11β-OH) es la segunda causa más común de las formas clásicas de hiperplasia suprarrenal congénita (HSC) (5–8% de los casos). Clínicamente se caracteriza por virilización e hipertensión arterial. El objetivo de este estudio es describir las características clínicas, bioquímicas, genéticas y la evolución de los pacientes seguidos en nuestro centro. Pacientes y métodos: Estudio observacional longitudinal, retrospectivo y descriptivo. Criterios de inclusión: clínica de virilización, 11-desoxicortisol elevado en plasma y estudio del gen CYP11B1 con variantes patogénicas y probablemente patogénicas. Resultados: Se identificaron 6 pacientes (1H, 5 M) pertenecientes a 4 familias. La edad media al diagnóstico de los 4 pacientes índice fue de 2.3 años. Las pacientes 46,XX mostraron grados variables de virilización al diagnóstico, predominando el estadio 5 de Prader, con un caso de asignación de género masculino al nacimiento. Todos los pacientes presentaron aumento de las concentraciones séricas de17-hidroxiprogesterona y testosterona. El 50% de los pacientes han desarrollado hipertensión arterial, con una mediana de edad de 9,3 años. Tres pacientes 46,XX han alcanzado talla final con una mediana de 154 cm. Se encontraron 6 variantes diferentes distribuidas a lo largo del gen CYP11B1, 5 de las cuales son variantes no descritas previamente (c.595 G > A, c.710 T > C, c.1156delG, c.395 + 2dupT, c.1159dupA). Conclusiones: Los pacientes con formas clásicas de HSC por déficit de 11β-OH presentan una gran heterogeneidad en la expresión clínica. El diagnóstico y el tratamiento precoces son importantes para prevenir complicaciones y mejorar los resultados a largo plazo. |
| format | Article |
| id | doaj-art-2aef4434a3044f7a951d19f5112ecf87 |
| institution | OA Journals |
| issn | 2341-2879 |
| language | Spanish |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Anales de Pediatría (English Edition) |
| spelling | doaj-art-2aef4434a3044f7a951d19f5112ecf872025-08-20T02:14:26ZspaElsevierAnales de Pediatría (English Edition)2341-28792025-02-01102250374710.1016/j.anpede.2025.503747Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomesElida Mercado Santis0Ariadna Campos1Paula Fernández2Josep Oriola3Diego Yeste4Víctor Pérez5María Clemente6Endocrinología Pediátrica, Hospital Universitario Vall d’Hebron Barcelona, Universidad Autónoma de Barcelona, Barcelona, Spain; Corresponding author.Endocrinología Pediátrica, Hospital Universitario Vall d’Hebron, Universidad Autónoma de Barcelona, Barcelona, SpainÁrea de Genética Clínica y Molecular, Hospital Universitario Vall d’Hebron, Barcelona, SpainCentro de Diagnóstico Biomédico – Bioquímica y Genética Molecular, Hospital Clínic Barcelona, Barcelona, SpainEndocrinología Pediátrica, Hospital Universitario Vall d’Hebron, CIBERER Barcelona, Univesidad Autónoma de Barcelona, Barcelona, SpainNefrología Pediátrica, Hospital Universitario Vall d’Hebron, Barcelona, SpainEndocrinología Pediátrica, Hospital Universitario Vall d’Hebron, CIBERER Barcelona, Univesidad Autónoma de Barcelona, Barcelona, SpainIntroduction: 11β-hydroxylase (11β-OH) deficiency is the second most frequent cause of classic congenital adrenal hyperplasia (CAH) (5%–8% of cases). Clinically, it is characterized by virilization and arterial hypertension. The objective of this study was to describe the clinical, biochemical and genetic characteristics classic 11β-OH deficiency in patients managed in our hospital and its outcomes. Patients and methods: Retrospective longitudinal, observational and descriptive study. Inclusion criteria: Patients with clinical features of virilization, high levels of 11-deoxycortisol and study of CYP11B1 gene with detection of pathogenic and likely pathogenic variants. Results: We identified 6 patients (1 male, 5 female) from 4 families. In the 4 index cases, the median age at diagnosis was 2.3 years. The 46,XX patients exhibited a variable degree of virilization at diagnosis, with a predominance of Prader stage V, and one case of male sex assignment at birth. All patients had elevated serum concentrations of 17-hydroxyprogesterone and testosterone. Fifty percent of the patients had developed arterial hypertension during the follow-up, with onset at a median age of 9.3 years. Three 46,XX patients reached a median final height of 154 cm. Six different variants of theCYP11B1 gene were identified, 5 of which were novel variants (c.595 G > A, c.710 T > C, c.1156delG, c.395 + 2dupT, c.1159dupA). Conclusions: There is considerable heterogeneity in the clinical presentation of patients with CAH due to 11β-OH deficiency. Early diagnosis and treatment are important to prevent complications and improve long-term outcomes. We report 6 different variants of the CYP11B1 gene, including 5 novel variants. Resumen: Introducción: La deficiencia de 11β-hidroxilasa (11β-OH) es la segunda causa más común de las formas clásicas de hiperplasia suprarrenal congénita (HSC) (5–8% de los casos). Clínicamente se caracteriza por virilización e hipertensión arterial. El objetivo de este estudio es describir las características clínicas, bioquímicas, genéticas y la evolución de los pacientes seguidos en nuestro centro. Pacientes y métodos: Estudio observacional longitudinal, retrospectivo y descriptivo. Criterios de inclusión: clínica de virilización, 11-desoxicortisol elevado en plasma y estudio del gen CYP11B1 con variantes patogénicas y probablemente patogénicas. Resultados: Se identificaron 6 pacientes (1H, 5 M) pertenecientes a 4 familias. La edad media al diagnóstico de los 4 pacientes índice fue de 2.3 años. Las pacientes 46,XX mostraron grados variables de virilización al diagnóstico, predominando el estadio 5 de Prader, con un caso de asignación de género masculino al nacimiento. Todos los pacientes presentaron aumento de las concentraciones séricas de17-hidroxiprogesterona y testosterona. El 50% de los pacientes han desarrollado hipertensión arterial, con una mediana de edad de 9,3 años. Tres pacientes 46,XX han alcanzado talla final con una mediana de 154 cm. Se encontraron 6 variantes diferentes distribuidas a lo largo del gen CYP11B1, 5 de las cuales son variantes no descritas previamente (c.595 G > A, c.710 T > C, c.1156delG, c.395 + 2dupT, c.1159dupA). Conclusiones: Los pacientes con formas clásicas de HSC por déficit de 11β-OH presentan una gran heterogeneidad en la expresión clínica. El diagnóstico y el tratamiento precoces son importantes para prevenir complicaciones y mejorar los resultados a largo plazo.http://www.sciencedirect.com/science/article/pii/S2341287925000304Hiperplasia suprarrenal congénitaDeficiencia de 11β-hidroxilasaGen CYP11B1Hipertensión arterial |
| spellingShingle | Elida Mercado Santis Ariadna Campos Paula Fernández Josep Oriola Diego Yeste Víctor Pérez María Clemente Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomes Anales de Pediatría (English Edition) Hiperplasia suprarrenal congénita Deficiencia de 11β-hidroxilasa Gen CYP11B1 Hipertensión arterial |
| title | Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomes |
| title_full | Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomes |
| title_fullStr | Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomes |
| title_full_unstemmed | Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomes |
| title_short | Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomes |
| title_sort | congenital adrenal hyperplasia due to 11 beta hydroxylase deficiency clinical biochemical and molecular characteristics and long term outcomes |
| topic | Hiperplasia suprarrenal congénita Deficiencia de 11β-hidroxilasa Gen CYP11B1 Hipertensión arterial |
| url | http://www.sciencedirect.com/science/article/pii/S2341287925000304 |
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