{"orpha":90793,"name":"Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CAH due to 17-alpha-hydroxylase deficiency","Combined 17-hydroxylase/17,20-lyase deficiency"],"definition":"A rare form of congenital adrenal hyperplasia due to 17-alpha-hydroxylase (CYP17A1) deficiency and characterized by glucocorticoid deficiency, mineralocorticoid excess leading to hypokalemic hypertension and sex steroid deficiency (hypergonadotrophic hypogonadism). Undervirilization and even female phenotype in 46,XY males, primary amenorrhea in females and lack of pubertal development in both sexes is common. Residual CYP17A1 activity is associated with the severity of this condition with a large spectrum of variability, from presenting in early infancy, to unusually mild courses with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-90793/","orphanet_url":"https://www.orpha.net/en/disease/detail/90793","names":{"fr":{"name":"Hyperplasie congénitale des surrénales par déficit en 17-alpha-hydroxylase","synonyms":["Déficit combiné en 17-hydroxylase/17,20-lyase","HCS par déficit en 17-alpha-hydroxylase"],"definition":"Forme rare d'hyperplasie congénitale des surrénales par déficit en 17-alpha-hydroxylase (CYP17A1), caractérisée par un déficit en glucocorticoïdes, un excès de minéralocorticoïdes entraînant une hypertension avec hypokaliémie et un déficit en stéroïdes sexuels (hypogonadisme hypergonadotrophique). L'hypovirilisation et même un phénotype féminin chez les hommes avec un caryotype 46,XY, une aménorrhée primaire chez la femme et une absence de développement pubertaire chez l'homme et la femme sont fréquents. L'activité résiduelle de CYP17A1 est associée à la sévérité de la maladie, dont le spectre varie considérablement d'une présentation pendant la petite enfance à des formes exceptionnellement légères avec déficit isolé en stéroïdes sexuels mais test de stimulation à l'ACTH normal chez les patients adultes."},"de":{"name":"Nebennierenhyperplasie, kongenitale, durch 17-alpha-Hydroxylase-Mangel","synonyms":["CAH durch 17-alpha-Hydroxylase-Mangel","Kombinierter 17-Hydroxylase/17,20-Lyase-Mangel","Kongenitale adrenale Hyperplasie durch 17-alpha-Hydroxylase-Mangel"],"definition":"Eine seltene Form der kongenitalen Nebennierenhyperplasie, die auf einem Mangel an 17-alpha-Hydroxylase (CYP17A1) beruht und durch einen Glukokortikoidmangel, einen Mineralokortikoidüberschuss, der zu hypokaliämischer Hypertonie führt, und einen Mangel an Sexualsteroiden (hypergonadotropher Hypogonadismus) gekennzeichnet ist. Untervirilisierung und sogar ein weiblicher Phänotyp beim männlichem Karyotyp (46,XY), primäre Amenorrhoe bei Frauen und fehlende Pubertätsentwicklung bei beiden Geschlechtern sind häufig. Die Restaktivität von CYP17A1 wird mit dem Schweregrad dieser Erkrankung in Verbindung gebracht, wobei es ein großes Spektrum an Variabilität gibt, das von einem Auftreten im frühen Säuglingsalter bis hin zu ungewöhnlich milden Verläufen mit isoliertem Sexualsteroidmangel, aber normalem ACTH-stimuliertem Cortisol bei erwachsenen Patienten reicht."},"es":{"name":"Hiperplasia suprarrenal congénita por deficiencia de 17-alfa-hidroxilasa","synonyms":["CAH por deficiencia de 17-alfa-hidroxilasa","Deficiencia combinada 17-hidroxilasa/17,20-liasa"],"definition":"Es una forma poco frecuente de hiperplasia suprarrenal congénita debida a un déficit de 17-alfa-hidroxilasa (CYP17A1) y caracterizada por deficiencia de glucocorticoides, exceso de mineralocorticoides que conduce a hipertensión hipopotasémica y deficiencia de esteroides sexuales (hipogonadismo hipergonadotrófico). Es común la subvirilización e incluso el fenotipo femenino en los varones 46,XY, la amenorrea primaria en las mujeres y la ausencia de desarrollo puberal en ambos sexos. La actividad residual de CYP17A1 se asocia con la gravedad de esta afección con un amplio espectro de variabilidad, desde la presentación en la primera infancia hasta cursos inusualmente leves con deficiencia aislada de esteroides sexuales pero cortisol normal estimulado por ACTH en pacientes adultos."},"it":{"name":"Iperplasia congenita del surrene da deficit di 17-alfa-idrossilasi","synonyms":["CAH da deficit di 17-alfa-idrossilasi","Deficit combinato di 17-idrossilasi/17,20-liasi"],"definition":"Si tratta di una forma rara di iperplasia congenita del surrene, causata da un deficit di 17-alfa-idrossilasi (CYP17A1), e caratterizzata da un deficit di glucocorticoidi, eccesso di mineralcorticoidi che esita nell'ipertensione ipokaliemica, e dal deficit degli steroidi sessuali (ipogonadismo ipergonadotropo). Sono comuni la scarsa virilizzazione e il fenotipo femminile nei maschi con cariotipo 46,XY, l'amenorrea primitiva nelle femmine e il mancato sviluppo puberale in entrambi i sessi. L'attività residua di CYP17A1 correla con la gravità della malattia, che è molto variabile e comprende l'esordio nella prima infanzia, fino a quadri clinici insolitamente lievi con deficit isolato degli steroidi sessuali ma normale cortisolo stimolato dall'ACTH negli adulti."},"nl":{"name":"Congenitale adrenale hyperplasie door deficiëntie van 17-alfa-hydroxylase","synonyms":["CAH door deficiëntie van 17-alfa-hydroxylase","Congenitale bijnierhyperplasie door deficiëntie van 17-alfa-hydroxylase","Gecombineerde deficiëntie van 17-hydroxylase/17,20-lyase"],"definition":"Een zeldzame vorm van congenitale adrenale hyperplasie door deficiëntie van 17-alfa-hydroxylase (CYP17A1), gekenmerkt door deficiëntie van glucocorticoïd, overmaat aan mineralocorticoïd die leidt tot hypokaliëmische hypertensie, en deficiëntie van geslachtshormonen (hypergonadotroop hypogonadisme). Ondervirilisatie en zelfs vrouwelijk fenotype bij 46,XY-mannen, primaire amenorroe bij vrouwen, en gebrek aan puberale ontwikkeling bij beide geslachten zijn gangbaar. Residuele CYP17A1-activiteit is geassocieerd met de ernst van deze aandoening, die grote variabiliteit vertoont, gaande van presentatie in de vroege zuigelingentijd, tot ongewoon mild verloop met geïsoleerde deficiëntie van geslachtshormoon maar normale ACTH-gestimuleerd cortisol bij volwassen patiënten."},"pt":{"name":"Hiperplasia supra-renal congénita por deficiência de 17-alfa-hidroxilase","synonyms":["CAH por deficiência de 17-alfa-hidroxilase","Deficiência combinada de 17-hidroxilase/17,20-liase"],"definition":"Forma rara de hiperplasia supra-renal congénita devido à deficiência de 17-alfa-hidroxilase (CYP17A1) e caracterizada por deficiência de glicocorticóides, excesso de mineralocorticóides levando a hipertensão hipocaliémica e deficiência de esteróides sexuais (hipogonadismo hipergonadotrófico). É comum a subvirilização e até mesmo o fenótipo feminino em homens 46,XY, amenorreia primária em mulheres e falha no desenvolvimento pubertário em ambos os sexos. A atividade residual do CYP17A1 está associada à expressão de gravidade da doença com uma ampla variabilidade, desde a apresentação clínica na primeira infância a casos ligeiros com deficiência isolada de esteróides sexuais, mas com produção normal de cortisol quando estimulado por ACTH em doentes adultos."},"pl":{"name":"Wrodzony przerost nadnerczy spowodowany niedoborem 17-alfa-hydroksylazy","synonyms":["CAH spowodowany niedoborem 17-alfa-hydroksylazy","Złożony Niedobór 17-hydroksylazy/17,20-liazy"]},"cs":{"name":"Vrozená adrenální hyperplázie způsobená deficitem 17-alfa-hydroxylázy","synonyms":["Kombinovaný deficit 17-hydroxylázy/17,20-lyázy"]},"uk":{"name":"Вроджена гіперплазія надниркових залоз внаслідок дефіциту 17-альфа-гідроксилази","synonyms":["АГС внаслідок дефіциту 17-альфа-гідроксилази","Поєднаний дефіцит 17-гідроксилази/17,20-ліази"],"definition":"A rare form of congenital adrenal hyperplasia due to 17-alpha-hydroxylase (CYP17A1) deficiency and characterized by glucocorticoid deficiency, mineralocorticoid excess leading to hypokalemic hypertension and sex steroid deficiency (hypergonadotrophic hypogonadism). Undervirilization and even female phenotype in 46,XY males, primary amenorrhea in females and lack of pubertal development in both sexes is common. Residual CYP17A1 activity is associated with the severity of this condition with a large spectrum of variability, from presenting in early infancy, to unusually mild courses with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients."},"zh":{"name":"17α-羟化酶缺乏所致先天性肾上腺皮质增生症","synonyms":["17-羟化酶/17,20-裂解酶联合缺乏"]},"tr":{"name":"17-alfa-hidroksilaz eksikliğine bağlı doğumsal adrenal hiperplazi","synonyms":["17-alfa-hidroksilaz eksikliğine bağlı CAH","Kombine 17-hidroksilaz / 17,20-liyaz eksikliği"]}},"xrefs":[{"source":"OMIM","code":"202110","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E25.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5A71.01","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"587903316"},{"source":"MONDO","code":"0008730","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C538237","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0268285","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"1469","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":90786,"name":"46,XY difference of sex development due to adrenal and testicular steroidogenesis defect","classifications":[147,156,185,193,205,233]},{"orpha":418,"name":"Congenital adrenal hyperplasia","classifications":[156,193]},{"orpha":400018,"name":"Rare female infertility due to adrenal disorder of genetic origin","classifications":[156]},{"orpha":399849,"name":"Rare female infertility due to an adrenal disorder","classifications":[201]},{"orpha":485382,"name":"Rare genetic premature ovarian failure","classifications":[156]},{"orpha":399584,"name":"Rare male infertility due to adrenal disorder","classifications":[201]},{"orpha":399994,"name":"Rare male infertility due to adrenal disorder of genetic origin","classifications":[156]},{"orpha":95710,"name":"Rare non-acquired premature ovarian failure","classifications":[193,205]}],"children":[],"genes":[{"symbol":"CYP17A1","name":"cytochrome P450 family 17 subfamily A member 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"2593","ensembl":"ENSG00000148795","omim":"609300","loci":["10q24.32"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 1 000 000","value":0.1,"area":"Europe","status":"Validated","source":"[EXPERT]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-04-02","source":"20170344[PMID]_26862015[PMID]","terms":[{"hpo":"HP:0031074","label":"Abnormal response to ACTH stimulation test","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0500022","label":"Abnormal serum dehydroepiandrosterone level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008258","label":"Congenital adrenal hyperplasia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0040171","label":"Decreased serum testosterone concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000822","label":"Hypertension","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0032362","label":"Increased circulating corticosterone level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000837","label":"Increased circulating gonadotropin level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0032330","label":"Increased urinary 11-deoxycorticosterone level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008197","label":"Absence of pubertal development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008187","label":"Absence of secondary sex characteristics","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011749","label":"Adrenocorticotropic hormone excess","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008689","label":"Bilateral cryptorchidism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004319","label":"Decreased circulating aldosterone level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008163","label":"Decreased circulating cortisol level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003351","label":"Decreased circulating renin concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000144","label":"Decreased fertility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008232","label":"Elevated circulating follicle stimulating hormone level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011969","label":"Elevated circulating luteinizing hormone level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000771","label":"Gynecomastia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002900","label":"Hypokalemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031216","label":"Increased circulating progesterone","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000858","label":"Irregular menstruation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000026","label":"Male hypogonadism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000138","label":"Ovarian cyst","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000786","label":"Primary amenorrhea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002221","label":"Absent axillary hair","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002555","label":"Absent pubic hair","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000033","label":"Ambiguous genitalia, male","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000151","label":"Aplasia of the uterus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000048","label":"Bifid scrotum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040314","label":"Blind vagina","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008730","label":"Female external genitalia in individual with 46,XY karyotype","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003251","label":"Male infertility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000054","label":"Micropenis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003394","label":"Muscle spasm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010465","label":"Precocious puberty in females","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008207","label":"Primary adrenal insufficiency","frequency":"Occasional (29-5%)","criteria":null}]}}