{"frequencyBands":{"HP:0040280":[100,100],"HP:0040281":[80,99],"HP:0040282":[30,79],"HP:0040283":[5,29],"HP:0040284":[1,4],"HP:0040285":[0,0]},"page":{"columns":[{"gene":"","key":"MONDO:0012520/OMIM:610549","label":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","mondoId":"MONDO:0012520","onsetQualifier":null,"recordKeys":["0eb39d038e7304a9e72d5f9e7988955acf2a689ec4dbc3aa0f6bd256ad8d6320","1f4659a8dd7783922885393eee51be5546c09ea57cf726edc6274e7a84613cbe","33898f4ecacd5a4e23cf9760aaa3c026020e2752bb9d38d6197fc4cfae8c2f6e","3bb676811ff54b47538b0da930760b131955ddbab52c9a99507aa24d7d466ea4","5184bd3e509bed1582bbe99c249f30345d1ec69af444f1ff56cc77996d617c83","5ea321711162c605312cde700a1f6ddcc8b05d436ed82085dec09726cb237738","73ae6f83e0a00790b6e3a8612be420e1c7cdf54fbf6638646331d401db6ef3bc","97a8c9af6608ec227375f212f15b78e54c2ff8498a4dd8c26ff8637e223668e4","9e5dab82b6168dc1927b1ddab4a5c3a1831e4936224aec946aea0698cad23598","e68e226961af04081fc57e618cbd943367adc5ec19474630d85927342ece52af","eef60d67d78833ee372db2921df740b8b99fea9018d1b19a191a394f3e91c693"],"recordQualifiers":{},"scopeLabel":"OMIM:610549","sourceIds":["OMIM:610549"],"sourceScope":"This column retains the native source entry. It is not a pooled estimate for the umbrella condition."},{"gene":"","key":"MONDO:0012520/ORPHA:2297","label":"Insulin-resistance syndrome type A","mondoId":"MONDO:0012520","onsetQualifier":null,"recordKeys":["029bf542b7c5b4959eb1ba75e296ffa2573b7c9a9214d5e7e599ea4de3527b65","3bfcd4463d087634f4705b8397b9551ca1fbf03d2d2c6eef5268902e925a2b2b","a35f7aad823a8c68c556943f0d47290ba9a5ae858a8c81780c0469737d72d155","c9fff97f43f6a35713b115e048e0ff6581a1d67b3eee63e65da2d2578828ea64","cd41bc8bce4bf8d3cb7176ae21ec791863565a14afb1eb0be0872fc7756835eb","eb362f28aea724ab5658deba25ee4d05c8a2f4a38072de2c7fd85f341640e416","f8a6bd3a97db1d679581a58811d26f2744d7828a4362725465d4c5b55bc7bd8d"],"recordQualifiers":{},"scopeLabel":"ORPHA:2297","sourceIds":["ORPHA:2297"],"sourceScope":"This column retains the native source entry. It is not a pooled estimate for the umbrella condition."}],"comparison":{"collapseColumnsLabel":"Show initial comparisons","defaultColumnKeys":["MONDO:0012520/OMIM:610549","MONDO:0012520/ORPHA:2297"],"expandColumnsLabel":"Compare all source entries","intro":"Compare the original source entries. Different entries may describe different patient groups.","primaryFeatureIds":[],"scopeNoteHtml":"<p>Each column keeps its native condition scope. Initial features are displayed alphabetically, not ranked by clinical importance. Counts remain separate, and an empty cell does not mean a feature cannot occur.</p>"},"coverage":{"countRecords":11,"emptyColumnKeys":[],"hpoRelease":"2026-06-23","narrativeSourceChanges":[],"records":18,"sourceGroups":{"omim":0,"orphanet":7,"published":11}},"features":[{"hpoId":"HP:0000956","label":"Acanthosis nigricans","primary":false},{"hpoId":"HP:0005616","label":"Accelerated skeletal maturation","primary":false},{"hpoId":"HP:0000141","label":"Amenorrhea","primary":false},{"hpoId":"HP:0000823","label":"Delayed puberty","primary":false},{"hpoId":"HP:0025092","label":"Epidermal acanthosis","primary":false},{"hpoId":"HP:0008283","label":"Fasting hyperinsulinemia","primary":false},{"hpoId":"HP:0002230","label":"Generalized hirsutism","primary":false},{"hpoId":"HP:0007440","label":"Generalized hyperpigmentation","primary":false},{"hpoId":"HP:0001007","label":"Hirsutism","primary":false},{"hpoId":"HP:0000962","label":"Hyperkeratosis","primary":false},{"hpoId":"HP:0025691","label":"Impaired fasting glucose","primary":false},{"hpoId":"HP:0040270","label":"Impaired glucose tolerance","primary":false},{"hpoId":"HP:0030348","label":"Increased circulating androgen concentration","primary":false},{"hpoId":"HP:0000855","label":"Insulin resistance","primary":false},{"hpoId":"HP:0000831","label":"Insulin-resistant diabetes mellitus","primary":false},{"hpoId":"HP:0000147","label":"Polycystic ovaries","primary":false},{"hpoId":"HP:0001482","label":"Subcutaneous nodule","primary":false},{"hpoId":"HP:0005978","label":"Type II diabetes mellitus","primary":false}],"ledeHtml":"Type A insulin resistance syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body&#x27;s tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with type A insulin resistance syndrome, insulin resistance impairs blood glucose regulation and ultimately leads to a condition called diabetes mellitus, in which blood glucose levels can become dangerously high.","mondoId":"MONDO:0012520","records":[{"frequencyKind":"range","key":"029bf542b7c5b4959eb1ba75e296ffa2573b7c9a9214d5e7e599ea4de3527b65","raw":{"aspect":"P","body_system":"skin","disease_id":"ORPHA:2297","disease_name":"Insulin-resistance syndrome type A","evidence":"TAS","frequency_raw":"HP:0040281","hpo_id":"HP:0007440","is_excluded":false,"label":"Generalized hyperpigmentation","onset_id":null,"reference":"ORPHA:2297","source_release":"2026-06-23"},"sourceGroups":["orphanet"]},{"frequencyKind":"count","key":"0eb39d038e7304a9e72d5f9e7988955acf2a689ec4dbc3aa0f6bd256ad8d6320","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0000855","is_excluded":false,"label":"Insulin resistance","onset_id":null,"reference":"PMID:8288049","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"1f4659a8dd7783922885393eee51be5546c09ea57cf726edc6274e7a84613cbe","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"2/2","hpo_id":"HP:0040270","is_excluded":false,"label":"Impaired glucose tolerance","onset_id":null,"reference":"PMID:8288049;PMID:2544998","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"33898f4ecacd5a4e23cf9760aaa3c026020e2752bb9d38d6197fc4cfae8c2f6e","raw":{"aspect":"P","body_system":"skin","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"2/2","hpo_id":"HP:0000956","is_excluded":false,"label":"Acanthosis nigricans","onset_id":null,"reference":"PMID:8288049;PMID:2544998","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"3bb676811ff54b47538b0da930760b131955ddbab52c9a99507aa24d7d466ea4","raw":{"aspect":"P","body_system":"metabolic","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"0/1","hpo_id":"HP:0025691","is_excluded":true,"label":"Impaired fasting glucose","onset_id":null,"reference":"PMID:2544998","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"range","key":"3bfcd4463d087634f4705b8397b9551ca1fbf03d2d2c6eef5268902e925a2b2b","raw":{"aspect":"P","body_system":"skin","disease_id":"ORPHA:2297","disease_name":"Insulin-resistance syndrome type A","evidence":"TAS","frequency_raw":"HP:0040281","hpo_id":"HP:0000962","is_excluded":false,"label":"Hyperkeratosis","onset_id":null,"reference":"ORPHA:2297","source_release":"2026-06-23"},"sourceGroups":["orphanet"]},{"frequencyKind":"count","key":"5184bd3e509bed1582bbe99c249f30345d1ec69af444f1ff56cc77996d617c83","raw":{"aspect":"P","body_system":"endocrine","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0000831","is_excluded":false,"label":"Insulin-resistant diabetes mellitus","onset_id":null,"reference":"PMID:2544998","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"5ea321711162c605312cde700a1f6ddcc8b05d436ed82085dec09726cb237738","raw":{"aspect":"P","body_system":"skin","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0025092","is_excluded":false,"label":"Epidermal acanthosis","onset_id":null,"reference":"PMID:8288049","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"73ae6f83e0a00790b6e3a8612be420e1c7cdf54fbf6638646331d401db6ef3bc","raw":{"aspect":"P","body_system":"genitourinary","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0000147","is_excluded":false,"label":"Polycystic ovaries","onset_id":null,"reference":"PMID:8288049","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"97a8c9af6608ec227375f212f15b78e54c2ff8498a4dd8c26ff8637e223668e4","raw":{"aspect":"P","body_system":"genitourinary","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0000141","is_excluded":false,"label":"Amenorrhea","onset_id":null,"reference":"PMID:8288049","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"count","key":"9e5dab82b6168dc1927b1ddab4a5c3a1831e4936224aec946aea0698cad23598","raw":{"aspect":"P","body_system":"skin","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0001007","is_excluded":false,"label":"Hirsutism","onset_id":null,"reference":"PMID:8288049","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"range","key":"a35f7aad823a8c68c556943f0d47290ba9a5ae858a8c81780c0469737d72d155","raw":{"aspect":"P","body_system":"endocrine","disease_id":"ORPHA:2297","disease_name":"Insulin-resistance syndrome type A","evidence":"TAS","frequency_raw":"HP:0040281","hpo_id":"HP:0000823","is_excluded":false,"label":"Delayed puberty","onset_id":null,"reference":"ORPHA:2297","source_release":"2026-06-23"},"sourceGroups":["orphanet"]},{"frequencyKind":"range","key":"c9fff97f43f6a35713b115e048e0ff6581a1d67b3eee63e65da2d2578828ea64","raw":{"aspect":"P","body_system":"musculoskeletal","disease_id":"ORPHA:2297","disease_name":"Insulin-resistance syndrome type A","evidence":"TAS","frequency_raw":"HP:0040281","hpo_id":"HP:0005616","is_excluded":false,"label":"Accelerated skeletal maturation","onset_id":null,"reference":"ORPHA:2297","source_release":"2026-06-23"},"sourceGroups":["orphanet"]},{"frequencyKind":"range","key":"cd41bc8bce4bf8d3cb7176ae21ec791863565a14afb1eb0be0872fc7756835eb","raw":{"aspect":"P","body_system":"skin","disease_id":"ORPHA:2297","disease_name":"Insulin-resistance syndrome type A","evidence":"TAS","frequency_raw":"HP:0040281","hpo_id":"HP:0001482","is_excluded":false,"label":"Subcutaneous nodule","onset_id":null,"reference":"ORPHA:2297","source_release":"2026-06-23"},"sourceGroups":["orphanet"]},{"frequencyKind":"count","key":"e68e226961af04081fc57e618cbd943367adc5ec19474630d85927342ece52af","raw":{"aspect":"P","body_system":"endocrine","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"1/1","hpo_id":"HP:0030348","is_excluded":false,"label":"Increased circulating androgen concentration","onset_id":null,"reference":"PMID:8288049","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"range","key":"eb362f28aea724ab5658deba25ee4d05c8a2f4a38072de2c7fd85f341640e416","raw":{"aspect":"P","body_system":"endocrine","disease_id":"ORPHA:2297","disease_name":"Insulin-resistance syndrome type A","evidence":"TAS","frequency_raw":"HP:0040281","hpo_id":"HP:0005978","is_excluded":false,"label":"Type II diabetes mellitus","onset_id":null,"reference":"ORPHA:2297","source_release":"2026-06-23"},"sourceGroups":["orphanet"]},{"frequencyKind":"count","key":"eef60d67d78833ee372db2921df740b8b99fea9018d1b19a191a394f3e91c693","raw":{"aspect":"P","body_system":"endocrine","disease_id":"OMIM:610549","disease_name":"Diabetes mellitus, insulin-resistant, with acanthosis nigricans","evidence":"PCS","frequency_raw":"2/2","hpo_id":"HP:0008283","is_excluded":false,"label":"Fasting hyperinsulinemia","onset_id":null,"reference":"PMID:8288049;PMID:2544998","source_release":"2026-06-23"},"sourceGroups":["published"]},{"frequencyKind":"range","key":"f8a6bd3a97db1d679581a58811d26f2744d7828a4362725465d4c5b55bc7bd8d","raw":{"aspect":"P","body_system":"skin","disease_id":"ORPHA:2297","disease_name":"Insulin-resistance syndrome type A","evidence":"TAS","frequency_raw":"HP:0040281","hpo_id":"HP:0002230","is_excluded":false,"label":"Generalized hirsutism","onset_id":null,"reference":"ORPHA:2297","source_release":"2026-06-23"},"sourceGroups":["orphanet"]}],"referenceLabels":{},"references":{"causeHtml":"<ul><li><a href=\"https://medlineplus.gov/genetics/condition/type-a-insulin-resistance-syndrome\">Type A insulin resistance syndrome</a></li></ul>","identityNote":"MONDO cross-references identify native condition entries. Ancestor membership does not transfer phenotype values between groups.","importantHtml":""},"sections":[{"bodyHtml":"<p>Type A insulin resistance syndrome results from mutations in the INSR gene. This gene provides instructions for making a protein called an insulin receptor, which is found in many types of cells. Insulin receptors are embedded in the outer membrane surrounding the cell, where they attach (bind) to insulin circulating in the bloodstream. This binding triggers signaling pathways that influence many cell functions.</p><p>Most of the INSR gene mutations that cause type A insulin resistance syndrome lead to the production of a faulty insulin receptor that cannot transmit signals properly. Although insulin is present in the bloodstream, the defective receptors make it less able to exert its effects on cells and tissues. This severe resistance to the effects of insulin impairs blood glucose regulation and leads to diabetes mellitus. In females with type A insulin resistance syndrome, excess insulin in the bloodstream interacts with hormonal factors during adolescence to cause abnormalities of the menstrual cycle, ovarian cysts, and other features of the disorder.</p><p>This condition is designated as type A to distinguish it from type B insulin resistance syndrome. Although the two disorders have similar signs and symptoms, type B is not caused by INSR gene mutations; instead, it results from an abnormality of the immune system that blocks insulin receptor function.</p><p class=\"section-source\"><a href=\"https://medlineplus.gov/genetics/condition/type-a-insulin-resistance-syndrome/#causes\">MedlinePlus Genetics: Causes</a></p>","key":"forms","title":"What causes Type A insulin resistance syndrome?"},{"bodyHtml":"<p>Severe insulin resistance also underlies the other signs and symptoms of type A insulin resistance syndrome. In affected females, the major features of the condition become apparent in adolescence. Many affected females do not begin menstruation by age 16 (primary amenorrhea) or their periods may be light and irregular (oligomenorrhea). They develop cysts on the ovaries and excessive body hair growth (hirsutism). Most affected females also develop a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Unlike most people with insulin resistance, females with type A insulin resistance syndrome are usually not overweight.</p><p>The features of type A insulin resistance syndrome are more subtle in affected males. Some males have low blood glucose (hypoglycemia) as the only sign; others may also have acanthosis nigricans. In many cases, males with this condition come to medical attention only when they develop diabetes mellitus in adulthood.</p><p>Type A insulin resistance syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and Rabson-Mendenhall syndrome, are considered part of a spectrum. Type A insulin resistance syndrome represents the mildest end of the spectrum: its features often do not become apparent until puberty or later, and it is generally not life-threatening.</p><p class=\"section-source\">Source: <a href=\"https://medlineplus.gov/genetics/condition/type-a-insulin-resistance-syndrome\">MedlinePlus Genetics</a></p>","key":"overview","title":"Condition overview"}],"sharedSources":[],"slug":"type-a-insulin-resistance-syndrome","sourceDocuments":[{"name":"Type A insulin resistance syndrome","reviewed":"2014-12","sections":{"causes":{"fetchedAt":"2026-10-20T20:25:37.864512+00:00","label":"Causes","pageSha256":"d23845e1d6666df13779d2fcd59d2dd8576f9b9fc48a88c405530810b15deaf3","sourceUrl":"https://medlineplus.gov/genetics/condition/type-a-insulin-resistance-syndrome/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/type-a-insulin-resistance-syndrome"}],"sourceNote":"MedlinePlus descriptions and Causes; original HPO annotations.","takeawayHtml":"Cause explanations are from MedlinePlus Genetics. Feature values below retain their original sources and patient groups.","title":"Type A insulin resistance syndrome"},"schemaVersion":1}