{"orpha":98267,"name":"Genetic non-syndromic obesity","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Monogenic obesity due to a leptin-melanocortin pathway anomaly"],"definition":"A rare genetic disease characterized by early-onset severe obesity due to mutations in single genes acting on the development and function of the hypothalamus or the leptin-melanocortin pathway, leading to disruption of energy homeostasis and endocrine dysfunction. Patients present with a body mass index over three standard deviations above normal at less than five years of age, accompanied by a variety of signs and symptoms according to the mutated gene, including hyperphagia, insulin resistance, reduced basal metabolic rate, or hypogonadism, among others.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-98267/","orphanet_url":"https://www.orpha.net/en/disease/detail/98267","names":{"fr":{"name":"Obésité non syndromique génétique","synonyms":["Obésité monogénique due à une anomalie de la voie leptine-mélanocortine"],"definition":"Maladie génétique rare caractérisée par une obésité sévère à apparition précoce due à des mutations dans des gènes spécifiques agissant sur le développement et la fonction de l'hypothalamus ou sur la voie leptine-mélanocortine, entraînant une perturbation de l'homéostasie énergétique et un dysfonctionnement endocrinien. Les patients présentent un indice de masse corporelle supérieur à trois écarts-types au-dessus de la normale à l'âge de moins de cinq ans, accompagné, suivant le gène muté, de divers signes cliniques et symptômes, tels que l'hyperphagie, la résistance à l'insuline, la réduction du métabolisme de base ou l'hypogonadisme."},"de":{"name":"Adipositas, genetisch-bedingte nicht-syndromale","synonyms":["Monogenetische Adipositas durch Störung des Leptin-Melanocortin-Signalweges"],"definition":"Eine seltene genetische Erkrankung, die durch eine früh einsetzende schwere Adipositas gekennzeichnet ist, die auf Mutationen in einzelnen Genen zurückzuführen ist, die die Entwicklung und Funktion des Hypothalamus oder des Leptin-Melanocortin-Signalwegs beeinflussen und zu einer Störung der Energiehomöostase und einer endokrinen Dysfunktion führen. Die Patienten weisen im Alter von weniger als fünf Jahren einen um mehr als drei Standardabweichungen über dem Normalwert liegenden Gewebeverdichtungsindex auf, der je nach mutiertem Gen von einer Vielzahl von Anzeichen und Symptomen begleitet wird, darunter Hyperphagie, Insulinresistenz, verminderter Grundumsatz oder Hypogonadismus, um nur einige zu nennen."},"es":{"name":"Obesidad genética no sindrómica","synonyms":["Obesidad monogénica por una anomalía en la vía leptina-melanocortina"],"definition":"Es una enfermedad de origen genético y poco frecuente caracterizada por una obesidad grave de inicio temprano causada por mutaciones en unos genes únicos implicados en el desarrollo y la función del hipotálamo o en la vía leptina-melanocortina, resultando en la alteración de la homeostasis energética y en la disfunción endocrina. Los pacientes se presentan con un índice de masa corporal superior a tres desviaciones estándar por encima de la media antes de los cinco años de edad, acompañado de signos y síntomas variables según el gen mutado, incluyendo hiperfagia, resistencia a la insulina, tasa metabólica basal reducida o hipogonadismo, entre otros."},"it":{"name":"Obesità genetica non sindromica","synonyms":["Obesità monogenica da anomalia del percorso leptina-melanocortina"],"definition":"Si tratta di una malattia genetica rara, caratterizzata da obesità grave ad esordio precoce, causata dalle mutazioni di singoli geni che agiscono sullo sviluppo e sulla funzione dell'ipotalamo, o sulla via leptina-melanocortina, e causano un'alterazione dell'omeostasi energetica e una disfunzione endocrina. I pazienti presentano un indice di massa corporea di tre deviazioni standard sopra la norma prima dei cinque anni, associato a diversi segni clinici, a seconda gene mutato (iperfagia, insulino-resistenza, ridotto metabolismo basale e ipogonadismo)."},"nl":{"name":"Genetische niet-syndromale obesitas","synonyms":["Monogene obesitas als gevolg van een leptine-melanocortinepathway-anomalie"],"definition":"Een zeldzame, genetische ziekte, gekarakteriseerd door vroeg optredende, ernstige obesitas als gevolg van mutaties in afzonderlijke genen met een rol in ontwikkeling en functie van hypothalamus of leptine-melanocortine signaalweg, wat leidt tot disruptie van energiehomeostase en endocriene disfunctie. Patiënten vertonen een queteletindex die drie standaarddeviaties boven de normale waarde ligt op een leeftijd jonger dan vijf jaar, in combinatie met verschillende tekenen en symptomen naargelang het gemuteerde gen, waaronder hyperfagie, insulineresistentie, vertraagd basaal metabolisme, of hypogonadisme."},"pt":{"name":"Obesidade monogénica por anomalia da via leptina-melanocortina"},"pl":{"name":"Otyłość niesyndromiczna uwarunkowana genetycznie","synonyms":["Otyłość monogenowa z powodu anomalii szlaku leptyna-monokortyna"]},"cs":{"name":"Geneticky podmíněné nesyndromické obezity","synonyms":["Monogenní obezity způsobené anomálií signální dráhy leptin-melanokortin"]},"uk":{"name":"Генетично обумовлене несиндромне ожиріння","synonyms":["Моногенне ожиріння внаслідок аномалії лептин-меланокортинового шляху"],"definition":"A rare genetic disease characterized by early-onset severe obesity due to mutations in single genes acting on the development and function of the hypothalamus or the leptin-melanocortin pathway, leading to disruption of energy homeostasis and endocrine dysfunction. Patients present with a body mass index over three standard deviations above normal at less than five years of age, accompanied by a variety of signs and symptoms according to the mutated gene, including hyperphagia, insulin resistance, reduced basal metabolic rate, or hypogonadism, among others."},"zh":{"name":"遗传性非综合征型肥胖","synonyms":["瘦素-黑皮质素通路异常所致单基因性肥胖"],"definition":"本病为一种罕见的遗传性疾病，由于作用于下丘脑发育及功能或瘦素-黑素皮质素途径的单基因突变而导致的早发性严重肥胖，致使能量代谢紊乱和内分泌功能障碍。患者在不到5岁时的体重指数比正常水平高出3个标准差，根据不同的突变基因回伴有各种体征和症状，包括过度进食、胰岛素抵抗、基础代谢率降低或性腺功能减退等。"},"tr":{"name":"Genetik sendromik olmayan obezite","synonyms":["Bir leptin-melanokortin yolu anomalisine bağlı monojenik obezite"]}},"xrefs":[{"source":"ICD-10","code":"E66.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5B81.Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0020075","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5680229","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":97978,"name":"Rare endocrine disease"},"parents":[{"orpha":77828,"name":"Genetic obesity","classifications":[156,193]}],"children":[{"orpha":397615,"name":"Obesity due to CEP19 deficiency","type":"Etiological subtype"},{"orpha":369873,"name":"Obesity due to SIM1 deficiency","type":"Etiological subtype"},{"orpha":66628,"name":"Obesity due to congenital leptin deficiency","type":"Etiological subtype"},{"orpha":179490,"name":"Obesity due to congenital leptin resistance","type":"Etiological subtype"},{"orpha":329249,"name":"Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency","type":"Etiological subtype"}],"genes":[],"genes_via_subtypes":[{"symbol":"CEP19","name":"centrosomal protein 19","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"24268657[PMID]","hgnc":"28209","ensembl":"ENSG00000174007","omim":"615586","loci":["3q29"],"via":{"orpha":397615,"name":"Obesity due to CEP19 deficiency"}},{"symbol":"SH2B1","name":"SH2B adaptor protein 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"23160192[PMID]","hgnc":"30417","ensembl":"ENSG00000178188","omim":"608937","loci":["16p11.2"],"via":{"orpha":329249,"name":"Severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency"}},{"symbol":"SIM1","name":"SIM bHLH transcription factor 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"23778136[PMID]_23778139[PMID]","hgnc":"10882","ensembl":"ENSG00000112246","omim":"603128","loci":["6q16.3"],"via":{"orpha":369873,"name":"Obesity due to SIM1 deficiency"}},{"symbol":"LEP","name":"leptin","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26567097[PMID]","hgnc":"6553","ensembl":"ENSG00000174697","omim":"164160","loci":["7q32.1"],"via":{"orpha":66628,"name":"Obesity due to congenital leptin deficiency"}}],"inheritance":["Not applicable"],"onset":["Childhood","Infancy"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Annual incidence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":null}