Deficiencia de Aromatasa

Descripción General

Epidemiología

• Prevalencia desconocida
• Hasta la fecha se han registrado alrededor de 30 casos en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum todo el mundo.

Genética

• Cariotipo: normal
• Etiología: mutación en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el gen CYP19A1, que desempeña un papel importante en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la síntesis de la enzima aromatasa
• Patrón de herencia: autosómico recesivo

Fisiopatología

• La enzima aromatasa es necesaria para convertir los LOS Neisseria andrógenos (incluida la testosterona) en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum estrógenos.
  • Normalmente, la aromatasa está presente en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity, los LOS Neisseria ovarios, los LOS Neisseria testículos, el tejido adiposo, la piel y el cerebro.
  • Los LOS Neisseria niveles de estrógeno se mantienen gracias a la actividad de la aromatasa en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum los LOS Neisseria ovarios de las mujeres en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum edad fértil y en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el tejido adiposo de los LOS Neisseria hombres y las mujeres posmenopáusicas.
• La mutación provoca ↓ producción de la enzima aromatasa → deterioro de la biosíntesis de estrógenos debido a la incapacidad de convertir los LOS Neisseria andrógenos en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum estrógenos → ↓ estrógenos y ↑ testosterona
• La placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity de un feto en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum desarrollo con deficiencia de aromatasa también carece de aromatasa.
• La placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity no convierte los LOS Neisseria andrógenos precursores en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum estrógenos → el sulfato de dehidroepiandrosterona (DHEAS por sus siglas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum inglés) de las glándulas suprarrenales del feto se convierte en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum testosterona y androstenediona en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum lugar de estrógenos.
• Los LOS Neisseria andrógenos desinhibidos y excesivos provocan la virilización del feto femenino y de la madre.

Presentación Clínica

Fenotipo clínico

• Características de la madre:
  • La virilización comienza durante el embarazo, entre las semanas 12 y 30 de gestación:
    • Acné
    • Profundización de la voz
    • Hirsutismo (crecimiento excesivo de vello con patrón masculino)
    • Clitoromegalia
  • Los LOS Neisseria síntomas se resuelven espontáneamente poco después del parto.
• Características de las mujeres (46,XX):
  • Pseudohermafroditismo ( los LOS Neisseria genitales externos se parecen a los LOS Neisseria del sexo opuesto)
  • Genitales ambiguos/masculinos observados al AL Amyloidosis nacer
    • Fusión labioescrotal
    • Falo muy agrandado con un solo meato en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum su base
    • Presente en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la semana 12 de gestación
  • Órganos reproductores femeninos presentes
  • Crecimiento y desarrollo normales en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la infancia y la niñez
  • Signos de falta de estrógenos y exceso de testosterona que se notan en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la edad puberal
    • Ausencia del estirón
    • Virilización progresiva
    • Retraso o falta de inicio de la pubertad
    • Ausencia de desarrollo mamario
    • Amenorrea primaria
    • Hipogonadismo hipergonadotrópico: ↑ hormona foliculoestimulante ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle, por sus siglas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum inglés) y hormona luteinizante ( LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle, por sus siglas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum inglés) con niveles ↓ de estrógenos.
    • Clitoromegalia
    • Acné
    • Desarrollo normal del vello axilar y púbico
• Características de los LOS Neisseria hombres (46,XY):
  • Estatura alta con crecimiento lineal continuado en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la edad adulta
  • No hay un estirón en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la pubertad
  • Hábito corporal eunucoide (extremidades desproporcionadamente largas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum relación con el tronco)
  • Retraso en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum los LOS Neisseria cierres epifisarios
  • Genu valgum Genu valgum Genu valgum is a deformation of the knee joint(s) that creates angulation of the lower limb(s) toward the midline in the coronal plane. Children ages 1-5 years are commonly affected. Genu Valgum progresivo («rodillas arqueadas»)
  • Genitales externos masculinos normales
  • Desarrollo y maduración sexual normal
  • Puede tener libido baja en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la adultez
  • Posible criptorquidia (testículos no descendidos)
  • Niveles variables de espermatogénesis y fertilidad

Afecciones asociadas

• Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum hombres y mujeres por deficiencia de estrógenos
• Intolerancia a la glucosa/ diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
• Dislipidemia
• Obesidad
• Enfermedad del hígado graso
• Acantosis nigricans (piel engrosada y oscurecida)

Diagnóstico y Tratamiento

Diagnóstico

• Antecedente clínico y examen físico
• Laboratorios:
  • Mujeres embarazadas
    • ↓↓ Niveles de estriol Estriol A hydroxylated metabolite of estradiol or estrogen that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During pregnancy, a large amount of estriol is produced by the placenta. Isomers with inversion of the hydroxyl group or groups are called epiestriol. Noncontraceptive Estrogen and Progestins y estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins
    • ↑↑ Concentración de testosterona
  • Niñas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la infancia/niñez temprana
    • ↑ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
    • Niveles de estrógeno indetectables
  • Niñas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum edad puberal
    • Niveles de estrógeno indetectables
    • ↑↑ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle y LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
    • ↑ Testosterona y androstenediona
  • Varones
    • ↑ FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle y LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle
    • ↑ Testosterona
    • Niveles de estrógeno indetectables
    • ↑ Insulina basal
    • ↓ Relación baja de colesterol HDL/LDL con ↓↓ HDL
• Imagenología:
  • El urogenitograma puede mostrar el seno urogenital (solo una apertura/salida para ambos tractos).
  • El ultrasonido muestra ovarios poliquísticos agrandados.
  • Las radiografías de la pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy y las extremidades muestran la falta de fusión epifisaria.
• Pruebas genéticas

Tratamiento

• Mujeres:
  • Corrección quirúrgica de los LOS Neisseria genitales ambiguos y de los LOS Neisseria senos urogenitales cuando están presentes
  • Sustitución de estrógenos a partir de los LOS Neisseria 2 años de edad con un control cercano:
    • Mantiene la densidad ósea.
    • Disminuye la formación de quistes ováricos.
    • En EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum exceso, puede acelerar la edad ósea e inducir el desarrollo prematuro de las mamas.
  • El estrógeno aumenta en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la edad puberal (10–12 años) para inducir:
    • Desarrollo de las mamas
    • Ritmo de crecimiento (se puede alcanzar la altura normal con el tratamiento)
    • Ciclos menstruales
    • Regresión de quistes ováricos
    • Aumento de la densidad ósea
  • Terapia de reemplazo de progesterona agregada dentro de los LOS Neisseria 2 años de reemplazo de estrógeno a nivel puberal para prevenir la hiperplasia endometrial
  • Anticonceptivos orales combinados iniciados aproximadamente a los LOS Neisseria 14 años de edad para la terapia de mantenimiento
• Hombres:
  • Sustitución transdérmica de estradiol Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. Noncontraceptive Estrogen and Progestins a partir de los LOS Neisseria 14–16 años, o en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum el momento del diagnóstico
  • El reemplazo de estrógenos es necesario para:
    • Cierre epifisario
    • Aumentar y mantener la densidad ósea
    • Mejorar el deseo sexual
    • Mejorar la resistencia a la insulina
    • Mejorar el perfil de lípidos
    • Normalización de los LOS Neisseria niveles de LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle, FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle y testosterona
  • Sustitución de estrógenos de por vida
  • Es necesario vigilar el desarrollo de la ginecomastia.
• Todos los LOS Neisseria individuos:
  • Suplementos de calcio y vitamina D
  • Asesoramiento genético

Diagnóstico Diferencial

• Hermafroditismo verdadero: También conocido como trastorno ovotesticular del desarrollo sexual. La enfermedad se caracteriza por la presencia de una gónada ovotesticular que contiene elementos ováricos y testiculares. Los LOS Neisseria pacientes tienen genitales ambiguos al AL Amyloidosis nacer, con órganos reproductores masculinos y femeninos que pueden verse en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la imagenología. El cariotipo y la biopsia gonadal ayudan a confirmar el diagnóstico. El tratamiento consiste en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la reconstrucción quirúrgica, la extirpación de la gónada anormal y la terapia de sustitución hormonal.
• Hiperplasia suprarrenal congénita: Consiste en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum un grupo de trastornos autosómicos recesivos que causan una deficiencia de una enzima utilizada en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum la síntesis de cortisol Cortisol Glucocorticoids y/o aldosterona. Esta deficiencia da lugar a un aumento de la formación de andrógenos con virilización de los LOS Neisseria genitales externos femeninos y es la causa más común de genitales ambiguos en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum las mujeres con genotipo 46,XX. Todas las formas de hiperplasia suprarrenal congénita se caracterizan por niveles bajos de cortisol Cortisol Glucocorticoids, niveles elevados de hormona adrenocorticotrópica (ACTH, por sus siglas en EN Erythema nodosum is an immune-mediated panniculitis (inflammation of the subcutaneous fat) caused by a type IV (delayed-type) hypersensitivity reaction. It commonly manifests in young women as tender, erythematous nodules on the shins. Erythema Nodosum inglés) e hiperplasia suprarrenal. La corrección quirúrgica de los LOS Neisseria genitales ambiguos y la terapia de reemplazo de glucocorticoides de por vida son necesarias.