{"orpha":168558,"name":"46,XY difference of sex development-adrenal insufficiency due to CYP11A1 deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency","XY sex reversal-adrenal failure"],"definition":"A rare, genetic, developmental defect during embryogenesis disorder characterized by severe, early-onset, salt-wasting adrenal insufficiency and ambiguous/female external genitalia (irrespective of chromosomal sex) due to mutations in the <i>CYP11A1</i> gene. Milder cases may present delayed onset of adrenal gland dysfunction and genitalia phenotype may range from normal male to female in individuals with 46,XY karyotype. Imaging studies reveal hypoplastic/absent adrenal glands and biochemical findings include low serum cortisol, mineralocorticoids, androgens, and sodium, with elevated potassium levels.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-168558/","orphanet_url":"https://www.orpha.net/en/disease/detail/168558","names":{"fr":{"name":"Différence du développement sexuel 46,XY-insuffisance surrénalienne par déficit en CYP11A1","synonyms":["Anomalie du développement sexuel 46,XY-insuffisance surrénalienne par déficit en CYP11A1"],"definition":"Anomalie rare du développement embryonnaire, d'origine génétique, caractérisée par une insuffisance surrénalienne précoce sévère, avec perte de sel, et par la présence d'organes génitaux externes féminins/une ambiguïté des organes génitaux externes (indépendamment du sexe chromosomique), due à des mutations du gène <i>CYP11A1</i>. Les cas les plus légers présentent un dysfonctionnement tardif des glandes surrénales et le phénotype sexuel peut aller d'un phénotype masculin normal à un phénotype féminin chez les personnes de caryotype 46,XY. L'imagerie met en évidence une hypoplasie/absence des glandes surrénales, et les analyses biochimiques révèlent un faible taux sérique de cortisol, de minéralocorticoïdes, d'androgènes et de sodium, ainsi qu'un taux élevé de potassium."},"de":{"name":"Störung der Geschlechtsentwicklung 46,XY - Nebenniereninsuffizienz, durch CYP11A1-Mangel","synonyms":["XY-Geschlechtsumkehr - Nebennierenversagen"]},"es":{"name":"Desarrollo sexual diferente 46,XY-insuficiencia suprarrenal por deficiencia de CYP11A1","synonyms":["Cambio de sexo XY-insuficiencia suprarrenal","DSD 46,XY-insuficiencia suprarrenal por deficiencia de CYP11A1","Inversión sexual XY-insuficiencia suprarrenal","Trastorno del desarrollo sexual 46,XY-insuficiencia suprarrenal por deficiencia de CYP11A1"],"definition":"Es un defecto del desarrollo embrionario de origen genético y poco frecuente caracterizado por grave insuficiencia suprarrenal perdedora de sal de inicio temprano y genitales externos ambiguos / femeninos (independientemente del sexo cromosómico) debido a mutaciones en el gen <i>CYP11A1</i>. Los casos más leves pueden presentar un inicio tardío de la insuficiencia suprarrenal y el fenotipo genital puede variar de un varón normal a una mujer en individuos con cariotipo 46, XY. Los estudios de imagen muestran glándulas suprarrenales hipoplásicas / ausentes y los hallazgos bioquímicos incluyen niveles séricos bajos de cortisol, mineralocorticoides, andrógenos y sodio, con niveles de potasio elevados."},"it":{"name":"Disturbo dello sviluppo sessuale 46,XY - insufficienza surrenalica da deficit di CYP11A1","synonyms":["Reversione sessuale XY - insufficienza surrenalica"],"definition":"Il disturbo dello sviluppo sessuale 46,XY con insufficienza surrenalica da deficit di CYP11A1 è un difetto genetico raro dello sviluppo dell'embrione, caratterizzato da insufficienza surrenalica con grave perdita di sale, ad esordio precoce, e genitali esterni ambigui/femminili (indipendentemente dal sesso cromosomico). La malattia è causata da mutazioni nel gene CYP11A1. I pazienti affetti dalle forme più lievi presentano disfunzione delle ghiandole surrenali ad esordio più tardivo, mentre i i genitali possono essere maschili normali o femminili in soggetti con cariotipo 46,XY. Le immagini diagnostiche evidenziano ipoplasia/assenza delle ghiandole surrenali e gli esami biochimici livelli bassi di cortisolo, mineralcorticoidi, androgeni e sodio nel siero, associati ad un aumento dei valori del potassio."},"nl":{"name":"46,XY-geslachtsontwikkelingsstoornis - adrenale insufficiëntie door CYP11A1-deficiëntie","synonyms":["46,XY-geslachtsontwikkelingsstoornis - bijnierinsufficiëntie door CYP11A1-deficiëntie","XY-geslachtsomkering - bijnierfalen"],"definition":"46,XY geslachtsontwikkelingsstoornis - adrenale insufficiëntie door CYP11A1-deficiëntie is een zeldzaam, genetisch, ontwikkelingsdefect tijdens de embryogenese dat gekarakteriseerd wordt door ernstige, vroeg aanvangende bijnierschorsinsufficiëntie met zoutverlies en ambigue/vrouwelijke uitwendige genitaliën (ongeacht het chromosomale geslacht) als gevolg van mutaties in het gen <i>CYP11A1</i>. Mildere gevallen vertonen mogelijk vertraagde aanvang van disfunctie van de bijnier en het fenotype van de geslachtsorganen kan gaan van normaal mannelijk tot vrouwelijk bij individuen met een 46,XY karyotype. Beeldvormingsstudies tonen hypoplastische/afwezige bijnieren en biochemische bevindingen zijn onder meer lage gehaltes van cortisol, mineralocorticoïden, androgenen en natrium in het serum, en verhoogde kaliumgehaltes."},"pt":{"name":"Doença do desenvolvimento sexual 46,XY-insuficiência supra-renal por deficiência de CYP11A1","synonyms":["Inversão sexual XY-insuficiência supra-renal"]},"pl":{"name":"Zaburzenie różnicowania płci o kariotypie 46,XY - niewydolność nadnerczy z powodu deficytu CYP11A1","synonyms":["Odwrócenie płci XY - niewydolność nadnerczy"]},"cs":{"name":"Syndrom zahrnující 46,XY poruchu pohlavního vývoje a nedostatečnost nadledvin způsobenou deficitem CYP11A1","synonyms":["Syndrom zahrnující XY zvrat pohlaví a selhání nadledvin"]},"uk":{"name":"46,XY порушення статевої диференціації-недостатності надниркових залоз внаслідок дефіциту CYP11A1","synonyms":["46,XY порушення статевого розвитку - недостатність надниркових залоз внаслідок дефіциту CYP11A1","XY реверсія статі - надниркова недостатність"],"definition":"A rare, genetic, developmental defect during embryogenesis disorder characterized by severe, early-onset, salt-wasting adrenal insufficiency and ambiguous/female external genitalia (irrespective of chromosomal sex) due to mutations in the <i>CYP11A1</i> gene. Milder cases may present delayed onset of adrenal gland dysfunction and genitalia phenotype may range from normal male to female in individuals with 46,XY karyotype. Imaging studies reveal hypoplastic/absent adrenal glands and biochemical findings include low serum cortisol, mineralocorticoids, androgens, and sodium, with elevated potassium levels."},"zh":{"name":"46，XY性发育障碍伴 - CYP11A1缺乏所致肾上腺功能不全","synonyms":["XY性逆转-肾上腺衰竭"],"definition":"CYP11A1基因缺陷所致46，XY性发育障碍性肾上腺功能不全是一种罕见的遗传性胚胎发育障碍疾病，由CYP11A1基因突变所致，其主要临床表现为重度早发性耗盐型肾上腺功能不全和两性畸形或表型女性（与染色体性别无关）。46，XY核型的轻度患者可能表现为迟发性肾上腺功能不全，表型可为男性或女性。影像学表现为肾上腺发育不全或缺失，生化检查包括血清皮质醇降低、盐皮质激素降低、雄激素降低、血钠降低以及血钾升高。"},"tr":{"name":"CYP11A1 eksikliğine bağlı 46,XY cinsiyet gelişim bozukluğu-adrenal yetersizlik","synonyms":["XY cinsiyet değişimi-adrenal yetmezlik"]}},"xrefs":[{"source":"OMIM","code":"613743","qualifier":"NTBT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E25.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0013400","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5190811","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":101960,"name":"Genetic chronic primary adrenal insufficiency","classifications":[156,193]}],"children":[],"genes":[{"symbol":"CYP11A1","name":"cytochrome P450 family 11 subfamily A member 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"18182448[PMID]_15507506[PMID]_11502818[PMID]","hgnc":"2590","ensembl":"ENSG00000140459","omim":"118485","loci":["15q24.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant","Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":9.0,"area":"Worldwide","status":"Validated","source":"21880796[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_21880796[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2015-11-02","source":"21159840[PMID]_19116240[PMID]_16705068[PMID]_18182448[PMID]_11502818[PMID]_12161514[PMID]_15507506[PMID]_16044444[PMID]_22909024[PMID]_15180858[PMID]_14172080[PMID]_3706293[PMID]_11972529[PMID]_9207791[PMID]_22909024[PMID]_12136908[PMID]","terms":[{"hpo":"HP:0012244","label":"Abnormal sex determination","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012598","label":"Abnormal urine potassium concentration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003107","label":"Abnormality of cholesterol metabolism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001197","label":"Abnormality of prenatal development or birth","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010789","label":"Abnormality of the Leydig cells","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008187","label":"Absence of secondary sex characteristics","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001941","label":"Acidosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011749","label":"Adrenocorticotropic hormone excess","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000033","label":"Ambiguous genitalia, male","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000151","label":"Aplasia of the uterus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004319","label":"Decreased circulating aldosterone level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030349","label":"Decreased circulating androgen level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008163","label":"Decreased circulating cortisol level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000144","label":"Decreased fertility","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008734","label":"Decreased testicular size","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001944","label":"Dehydration","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008730","label":"Female external genitalia in individual with 46,XY karyotype","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007574","label":"Generalized bronze hyperpigmentation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007440","label":"Generalized hyperpigmentation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000771","label":"Gynecomastia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002153","label":"Hyperkalemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012605","label":"Hypernatriuria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002902","label":"Hyponatremia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002615","label":"Hypotension","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011106","label":"Hypovolemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003154","label":"Increased circulating ACTH level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000848","label":"Increased circulating renin level","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030369","label":"Induced vaginal delivery","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008073","label":"Low maternal serum estriol","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000037","label":"Male pseudohermaphroditism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001998","label":"Neonatal hypoglycemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000939","label":"Osteoporosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008207","label":"Primary adrenal insufficiency","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004349","label":"Reduced bone mineral density","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000127","label":"Renal salt wasting","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012245","label":"Sex reversal","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100779","label":"Urogenital sinus anomaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000835","label":"Adrenal hypoplasia","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:0001622","label":"Premature birth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000142","label":"Abnormality of the vagina","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008665","label":"Clitoral hypertrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012854","label":"Midshaft hypospadias","frequency":"Occasional (29-5%)","criteria":null}]}}