PedAM
Pediatric Disease Annotations & Medicines
| hyperinsulinism | ||||
| Disease ID | 715 |
|---|---|
| Disease | hyperinsulinism |
| Integrated Phenotype | (Waiting for update.) |
| Text Mined Phenotype | HPO | Name | Sentences' Count(Total Phenotypes:15) HP:0001943 | Hypoglycemia | 24 HP:0001987 | Hyperammonemia | 1 HP:0002664 | Neoplasia | 1 HP:0001998 | Low blood sugar in newborn | 1 HP:0000855 | Insulin resistance | 1 HP:0001520 | Birthweight > 90th percentile | 1 HP:0001873 | Low platelet count | 1 HP:0009800 | gestational diabetes | 1 HP:0000825 | Hyperinsulinaemic hypoglycaemia | 1 HP:0100842 | Septo-optic dysplasia | 1 HP:0001513 | Obesity | 1 HP:0008220 | Glucocorticoid insufficiency | 1 HP:0001511 | Prenatal onset growth retardation | 1 HP:0001988 | hypoglycemia, recurrent | 1 HP:0000833 | Glucose intolerance | 1 |
| Disease ID | 715 |
|---|---|
| Disease | hyperinsulinism |
| Manually Symptom | (Waiting for update.) |
| Text Mined Symptom | UMLS | Name | Sentences' Count(Total Symptoms:3) |
Manually Genotype(Total Text Mining Genotypes:0) |
|---|
| (Waiting for update.) |
All Snps(Total Genotypes:26) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| snpId | pubmedId | geneId | geneSymbol | diseaseId | sourceId | sentence | score | Year | geneSymbol_dbSNP | CHROMOSOME | POS | REF | ALT |
| rs104894236 | 20694718 | 3767 | KCNJ11 | umls:C0020459 | BeFree | A mutation in KCNJ11 causing human hyperinsulinism (Y12X) results in a glucose-intolerant phenotype in the mouse. | 0.008077243 | 2010 | KCNJ11 | 11 | 17388056 | G | T,A |
| rs11575937 | 11136544 | 4000 | LMNA | umls:C0020459 | BeFree | Through the use of focused DNA sequencing of positional candidate genes on chromosome 1q21, we discovered that FPLD results from mutations in LMNA (R482Q; OMIM 150330.0010), which is the gene that encodes nuclear lamins A and C. By stratifying members of extended FPLD pedigrees according to LMNA genotype, we found that hyperinsulinemia is present early in the course of the disease and that dyslipidemia (characterized by high triglycerides and depressed HDL cholesterol) precedes the development of glucose abnormalities. | 0.001357209 | 2000 | LMNA | 1 | 156136985 | G | A,T |
| rs11575937 | 11122771 | 4000 | LMNA | umls:C0020459 | BeFree | FPLD was recently discovered to result from mutated LMNA (R482Q; OMIM | |||||||
| 150330.0010), which is the gene encoding nuclear lamins A and C. Results from extended pedigrees indicate that dyslipidemia precedes the plasma glucose abnormalities in FPLD subjects with mutant LMNA, and that the hyperinsulinemia is present early in the course of the disease. | 0.001357209 | 2000 | LMNA | 1 | 156136985 | G | A,T | ||||||
| rs11575937 | 10810087 | 4000 | LMNA | umls:C0020459 | BeFree | Association between nuclear lamin A/C R482Q mutation and partial lipodystrophy with hyperinsulinemia, dyslipidemia, hypertension, and diabetes. | 0.001357209 | 2000 | LMNA | 1 | 156136985 | G | A,T |
| rs121913564 | 22463805 | 4160 | MC4R | umls:C0020459 | BeFree | Homozygous MC4R mutations, M161T and I316S, identified separately in 2 subjects (3.2%), were associated with severe obesity, hyperphagia, hyperleptinemia and hyperinsulinemia. | 0.124267125 | 2012 | MC4R | 18 | 60371403 | A | C |
| rs12970134 | 21372613 | 4160 | MC4R | umls:C0020459 | BeFree | In sum, our data support the associations of variants rs17782313 and rs12970134 near MC4R with early onset obesity and increased insulin levels. | 0.124267125 | 2011 | NA | 18 | 60217517 | G | A |
| rs137852671 | 12559865 | 6833 | ABCC8 | umls:C0020459 | BeFree | We have described a dominant heterozygous mutation--E1506K--in the sulfonylurea receptor 1 (SUR1) gene (ABCC8) in a Finnish family, which leads to congenital hyperinsulinaemia due to reduction of K(ATP)-channel activity. | 0.014320406 | 2003 | ABCC8 | 11 | 17394295 | C | T |
| rs137852671 | 23903354 | 6833 | ABCC8 | umls:C0020459 | BeFree | A mouse model of human hyperinsulinism produced by the E1506K mutation in the sulphonylurea receptor SUR1. | 0.014320406 | 2013 | ABCC8 | 11 | 17394295 | C | T |
| rs146695489 | 24080777 | 6833 | ABCC8 | umls:C0020459 | BeFree | Octreotide-induced long QT syndrome in a child with congenital hyperinsulinemia and a novel missense mutation (p.Met115Val) in the ABCC8 gene. | 0.014320406 | 2013 | ABCC8 | 11 | 17470170 | T | C |
| rs1718119 | 25719930 | 5027 | P2RX7 | umls:C0020459 | BeFree | In the Prevalence, Prediction, and Prevention of Diabetes in Botnia study, the minor allele in the missense functional variant rs1718119 (A348T) in P2RX7 was associated with increased insulin sensitivity and secretion, consistent with its known effect on increased pore function. | 0.000271442 | 2015 | P2RX7;LOC105370032 | 12 | 121177300 | G | T,A |
| rs17782313 | 21372613 | 4160 | MC4R | umls:C0020459 | BeFree | In sum, our data support the associations of variants rs17782313 and rs12970134 near MC4R with early onset obesity and increased insulin levels. | 0.124267125 | 2011 | NA | 18 | 60183864 | T | C |
| rs1801282 | 12370112 | 5468 | PPARG | umls:C0020459 | BeFree | Our results suggest that the Pro12Ala polymorphism of the PPARgamma-2 gene promotes peripheral deposition of adipose tissue and increased insulin sensitivity for a given BMI. | 0.009901391 | 2002 | PPARG | 3 | 12351626 | C | G |
| rs1801282 | 23748472 | 5468 | PPARG | umls:C0020459 | BeFree | We investigated individual and combined associations of Pro12Ala and His447His polymorphisms of PPARγ with PCOS susceptibility and its related traits (hyperinsulinemia, hyperandrogenemia and lipid parameters) in Indian women. | 0.009901391 | 2013 | PPARG | 3 | 12351626 | C | G |
| rs1801282 | 15853827 | 5468 | PPARG | umls:C0020459 | BeFree | The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is associated with a lower hirsutism score and increased insulin sensitivity in women with polycystic ovary syndrome. | 0.009901391 | 2005 | PPARG | 3 | 12351626 | C | G |
| rs1801282 | 20368233 | 5468 | PPARG | umls:C0020459 | BeFree | Pro12Ala, a missense mutation in exon 2 of PPARG, reduces transcriptional activity of PPARgamma2 and is shown to be associated with increased insulin sensitivity and protection from T2D. | 0.009901391 | 2010 | PPARG | 3 | 12351626 | C | G |
| rs1805192 | 12370112 | 5468 | PPARG | umls:C0020459 | BeFree | Our results suggest that the Pro12Ala polymorphism of the PPARgamma-2 gene promotes peripheral deposition of adipose tissue and increased insulin sensitivity for a given BMI. | 0.009901391 | 2002 | PPARG | 3 | 12379739 | C | G |
| rs1805192 | 20368233 | 5468 | PPARG | umls:C0020459 | BeFree | Pro12Ala, a missense mutation in exon 2 of PPARG, reduces transcriptional activity of PPARgamma2 and is shown to be associated with increased insulin sensitivity and protection from T2D. | 0.009901391 | 2010 | PPARG | 3 | 12379739 | C | G |
| rs1805192 | 23748472 | 5468 | PPARG | umls:C0020459 | BeFree | We investigated individual and combined associations of Pro12Ala and His447His polymorphisms of PPARγ with PCOS susceptibility and its related traits (hyperinsulinemia, hyperandrogenemia and lipid parameters) in Indian women. | 0.009901391 | 2013 | PPARG | 3 | 12379739 | C | G |
| rs1805192 | 15853827 | 5468 | PPARG | umls:C0020459 | BeFree | The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is associated with a lower hirsutism score and increased insulin sensitivity in women with polycystic ovary syndrome. | 0.009901391 | 2005 | PPARG | 3 | 12379739 | C | G |
| rs193922479 | NA | 3172 | HNF4A | umls:C0020459 | CLINVAR | NA | 0.124267125 | NA | HNF4A | 20 | 44424116 | C | T |
| rs2014355 | 21211036 | 3630 | INS | umls:C0020459 | BeFree | In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (β) = -3.8% (-6.3%;-1.3%), P = 0.003), reduced incremental area under the insulin curve (β = -3.6% (-6.3%;-0.9%), P = 0.009), reduced acute insulin response (β = -2.2% (-4.2%;0.2%), P = 0.03), and with increased insulin sensitivity ISIMatsuda (β = 2.9% (0.5%;5.2%), P = 0.02). | 0.192971713 | 2011 | ACADS | 12 | 120737721 | T | C |
| rs201682634 | 19151370 | 6833 | ABCC8 | umls:C0020459 | BeFree | Here we report that two hyperinsulinism-associated SUR1 missense mutations, R74W and E128K, surprisingly reduce channel inhibition by intracellular ATP, a gating defect expected to yield the opposite disease phenotype neonatal diabetes. | 0.014320406 | 2009 | ABCC8 | 11 | 17474956 | G | A |
| rs2241766 | 20388053 | 9370 | ADIPOQ | umls:C0020459 | BeFree | The risk of PCOS, hyperandrogenism in patients with PCOS and low serum adiponectin levels cannot be directly attributed to T45G adiponectin gene polymorphisms in exon 2, rather these polymorphisms may be associated with insulin resistance and hyperinsulinemia in PCOS. | 0.082909916 | 2010 | ADIPOQ;ADIPOQ-AS1 | 3 | 186853103 | T | G |
| rs386510633 | 19214805 | 4160 | MC4R | umls:C0020459 | BeFree | MC4R variants were detected in three patients: the known I169S variant was found in heterozygote state in two patients and a novel heterozygous Y302F mutation was detected in one 12-year-old girl (BMI = 34 kg/m(2), BMI z-score 2.7) who has been overweight since the second year of life and suffered from hyperinsulinemia (at the age of 12: fasting insulin 45 mU/ml, after oral glucose load max. | 0.124267125 | 2009 | NA | NA | NA | NA | NA |
| rs386510633 | 19214805 | 3630 | INS | umls:C0020459 | BeFree | MC4R variants were detected in three patients: the known I169S variant was found in heterozygote state in two patients and a novel heterozygous Y302F mutation was detected in one 12-year-old girl (BMI = 34 kg/m(2), BMI z-score 2.7) who has been overweight since the second year of life and suffered from hyperinsulinemia (at the age of 12: fasting insulin 45 mU/ml, after oral glucose load max. | 0.192971713 | 2009 | NA | NA | NA | NA | NA |
| rs587777732 | NA | 3172 | HNF4A | umls:C0020459 | CLINVAR | NA | 0.124267125 | NA | HNF4A;MIR3646 | 20 | 44406195 | C | T |
GWASdb Annotation(Total Genotypes:0) | |
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| (Waiting for update.) | |
GWASdb Snp Trait(Total Genotypes:0) | |
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| (Waiting for update.) | |
Mapped by lexical matching(Total Items:0) |
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| (Waiting for update.) |
Mapped by homologous gene(Total Items:0) |
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| (Waiting for update.) |
Chemical(Total Drugs:9) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| CUI | ChemicalName | ChemicalID | CasRN | DiseaseName | DiseaseID | DirectEvidence | PubMedIDs | ||
| C0020459 | allopurinol | D000493 | 315-30-0 | hyperinsulinism | MESH:D006946 | therapeutic | 19605544 | ||
| C0020459 | benazepril | C044946 | 86541-75-5 | hyperinsulinism | MESH:D006946 | therapeutic | 9725782 | ||
| C0020459 | metformin | D008687 | 657-24-9 | hyperinsulinism | MESH:D006946 | therapeutic | 18377884 | ||
| C0020459 | olanzapine | C076029 | 132539-06-1 | hyperinsulinism | MESH:D006946 | marker/mechanism | 11927762 | ||
| C0020459 | rosiglitazone | C089730 | - | hyperinsulinism | MESH:D006946 | therapeutic | 17697064 | ||
| C0020459 | streptozocin | D013311 | 18883-66-4 | hyperinsulinism | MESH:D006946 | marker/mechanism | 18377884 | ||
| C0020459 | troglitazone | C057693 | 97322-87-7 | hyperinsulinism | MESH:D006946 | marker/mechanism | 9389757 | ||
| C0020459 | troglitazone | C057693 | 97322-87-7 | hyperinsulinism | MESH:D006946 | therapeutic | 11889176 | ||
| C0020459 | valproic acid | D014635 | 99-66-1 | hyperinsulinism | MESH:D006946 | marker/mechanism | 19184102 | ||
FDA approved drug and dosage information(Total Drugs:4) | ||||||||
|---|---|---|---|---|---|---|---|---|
| DiseaseID | Drug_name | active_ingredients | strength | Dosage Form/Route | Marketing Status | TE code | RLD | RS |
| MESH:D006946 | zyprexa | olanzapine | 2.5MG | TABLET;ORAL | Prescription | AB | Yes | No |
| MESH:D006946 | zyprexa | olanzapine | 10MG/VIAL | INJECTABLE;INTRAMUSCULAR | Prescription | AP | Yes | Yes |
| MESH:D006946 | zyprexa | olanzapine | 2.5MG | TABLET;ORAL | Prescription | AB | Yes | No |
| MESH:D006946 | zyprexa | olanzapine | 10MG/VIAL | INJECTABLE;INTRAMUSCULAR | Prescription | AP | Yes | Yes |
FDA labeling changes(Total Drugs:4) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DiseaseID | Pediatric_Labeling_Date | Trade_Name | Generic_Name_or_Proper_Name | Indications Studied | Label Changes Summary | Product Labeling | BPCA(B) | PREA(P) | BPCA(B) and PREA(P) | Pediatric Rule (R) | Sponsor | Pediatric Exclusivity Granted Date | NNPS |
| MESH:D006946 | 08/14/2008 | zyprexa | olanzapine | schizophrenia; bipolar disorder | Safety and effectiveness have not been established for patients less than 18 years of age In an analysis of placebo-controlled olanzapine monotherapy studies of adolescent patients, including those with schizophrenia or bipolar disorder, olanzapine was associated with: oHyperglycemia - a statistically significantly greater mean change in fasting glucose levels compared to placebo oHyperlipidemia statistically significant increases compared to placebo in fasting triglycerides, fasting total cholesterol and fasting LDL cholesterol oWeight gain olanzapine treated patients gained an average of 4.6 kg, compared to an average of 0.3 kg in placebo-treated patients with a median exposure of 3 weeks; Average weight gain during long-term therapy was 7.4 kg | - | B | - | - | - | Lilly | 10/1/2007 | FALSE' |
| MESH:D006946 | 08/14/2008 | zyprexa | olanzapine | schizophrenia; bipolar disorder | Safety and effectiveness have not been established for patients less than 18 years of age In an analysis of placebo-controlled olanzapine monotherapy studies of adolescent patients, including those with schizophrenia or bipolar disorder, olanzapine was associated with: oHyperglycemia - a statistically significantly greater mean change in fasting glucose levels compared to placebo oHyperlipidemia statistically significant increases compared to placebo in fasting triglycerides, fasting total cholesterol and fasting LDL cholesterol oWeight gain olanzapine treated patients gained an average of 4.6 kg, compared to an average of 0.3 kg in placebo-treated patients with a median exposure of 3 weeks; Average weight gain during long-term therapy was 7.4 kg | - | B | - | - | - | Lilly | 10/1/2007 | FALSE' |
| MESH:D006946 | 4/12/2009 | zyprexa | olanzapine | Treatment of manic or mixed episodes of bipolar I disorder and schizophrenia in adolescents ages 13-17 | Extended schizophrenia and manic or mixed episodes of bipolar I disorder indications from adults to adolescents 1317 years of age Safety and effectiveness in children < 13 years of age have not been established Recommended starting dose for adolescents is lower than that for adults Compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin and hepatic transaminase levels Information on dosing, adverse reactions, pharmacokinetics, clinical studies | Labeling | B | - | - | - | Lilly | 10/1/2007 | TRUE' |
| MESH:D006946 | 4/12/2009 | zyprexa | olanzapine | Treatment of manic or mixed episodes of bipolar I disorder and schizophrenia in adolescents ages 13-17 | Extended schizophrenia and manic or mixed episodes of bipolar I disorder indications from adults to adolescents 1317 years of age Safety and effectiveness in children < 13 years of age have not been established Recommended starting dose for adolescents is lower than that for adults Compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin and hepatic transaminase levels Information on dosing, adverse reactions, pharmacokinetics, clinical studies | Labeling | B | - | - | - | Lilly | 10/1/2007 | TRUE' |