HHF4
MCID: HYP271
MIFTS: 52

Hyperinsulinemic Hypoglycemia, Familial, 4 (HHF4)

Categories: Blood diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hyperinsulinemic Hypoglycemia, Familial, 4

MalaCards integrated aliases for Hyperinsulinemic Hypoglycemia, Familial, 4:

Name: Hyperinsulinemic Hypoglycemia, Familial, 4 57 29 13 6 39 70
Hyperinsulinism Due to Glutamodehydrogenase Deficiency 12 20 58 6
Familial Hyperinsulinemic Hypoglycemia 4 12 72 15
Hhf4 57 12 72
Hyperinsulinemic Hypoglycemia Due to Short Chain 3-Hydroxylacyl-Coa Dehydrogenase Deficiency 12 58
Hyperinsulinism Due to Short Chain 3-Hydroxylacyl-Coa Dehydrogenase Deficiency 12 58
Hyperinsulinism Due to Schad Deficiency 12 58
Congenital Hyperinsulinism 72 70
Persistent Hyperinsulinemic Hypoglycemia of Infancy 72
3-Hydroxyacyl-Coa Dehydrogenase Deficiency 70
Schad Deficiency 58
Phhi 72

Characteristics:

Orphanet epidemiological data:

58
hyperinsulinism due to short chain 3-hydroxylacyl-coa dehydrogenase deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
genetic heterogeneity (see hhf1 )


HPO:

31
hyperinsulinemic hypoglycemia, familial, 4:
Inheritance autosomal recessive inheritance heterogeneous


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Hyperinsulinemic Hypoglycemia, Familial, 4

UniProtKB/Swiss-Prot : 72 Familial hyperinsulinemic hypoglycemia 4: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur. HHF4 should be easily recognizable by analysis of acylcarnitine species and that this disorder responds well to treatment with diazoxide. It provides the first 'experiment of nature' that links impaired fatty acid oxidation to hyperinsulinism and that provides support for the concept that a lipid signaling pathway is implicated in the control of insulin secretion.

MalaCards based summary : Hyperinsulinemic Hypoglycemia, Familial, 4, also known as hyperinsulinism due to glutamodehydrogenase deficiency, is related to hyperinsulinemic hypoglycemia, familial, 3 and hyperinsulinemic hypoglycemia, familial, 2. An important gene associated with Hyperinsulinemic Hypoglycemia, Familial, 4 is HADH (Hydroxyacyl-CoA Dehydrogenase). The drugs lanreotide and Angiopeptin have been mentioned in the context of this disorder. Affiliated tissues include pancreas, kidney and pituitary, and related phenotypes are decreased 3-hydroxyacyl-coa dehydrogenase level and neonatal hypotonia

Disease Ontology : 12 A hyperinsulinemic hypoglycemia characterized by autosomal recessive inheritance of hyperinsulinemic hypoglycemia with seizures that has material basis in mutation in the HADH gene on chromosome 4q25.

More information from OMIM: 609975 PS256450

Related Diseases for Hyperinsulinemic Hypoglycemia, Familial, 4

Diseases in the Hyperinsulinemic Hypoglycemia family:

Hyperinsulinemic Hypoglycemia, Familial, 1 Hyperinsulinemic Hypoglycemia, Familial, 2
Hyperinsulinemic Hypoglycemia, Familial, 3 Hyperinsulinemic Hypoglycemia, Familial, 6
Hyperinsulinemic Hypoglycemia, Familial, 5 Hyperinsulinemic Hypoglycemia, Familial, 4
Hyperinsulinemic Hypoglycemia, Familial, 7

Diseases related to Hyperinsulinemic Hypoglycemia, Familial, 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 133)
# Related Disease Score Top Affiliating Genes
1 hyperinsulinemic hypoglycemia, familial, 3 32.2 CEP55 AURKB
2 hyperinsulinemic hypoglycemia, familial, 2 11.9
3 hyperinsulinemic hypoglycemia, familial, 1 11.9
4 hyperinsulinemic hypoglycemia, familial, 5 11.7
5 3-hydroxyacyl-coa dehydrogenase deficiency 11.6
6 hyperinsulinemic hypoglycemia, familial, 6 11.3
7 hyperinsulinemic hypoglycemia 11.1
8 hypoglycemia 11.1
9 3-alpha hydroxyacyl-coa dehydrogenase deficiency 11.1
10 hyperinsulinism 10.8
11 autosomal recessive disease 10.5
12 carbonic anhydrase va deficiency, hyperammonemia due to 10.3
13 insulinoma 10.3
14 hyperglycemia 10.3
15 maturity-onset diabetes of the young 10.3
16 permanent neonatal diabetes mellitus 10.3
17 neonatal diabetes 10.3
18 diabetes mellitus, permanent neonatal, 1 10.3
19 beckwith-wiedemann syndrome 10.2
20 ocular motor apraxia 10.2
21 gallbladder disease 1 10.2
22 abdominal obesity-metabolic syndrome 1 10.2
23 diabetes mellitus, transient neonatal, 3 10.2
24 cyanosis, transient neonatal 10.2
25 metabolic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 10.2
26 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.2
27 transient neonatal diabetes mellitus 10.2
28 glucose intolerance 10.2
29 hypertrichosis 10.2
30 adenoma 10.2
31 neuroblastoma 10.2
32 diabetes mellitus 10.2
33 paternal uniparental disomy 10.2
34 overgrowth syndrome 10.2
35 atrial standstill 1 10.1
36 kabuki syndrome 1 10.1
37 acute insulin response 10.1
38 alacrima, achalasia, and mental retardation syndrome 10.1
39 monogenic diabetes 10.1
40 hypotonia 10.1
41 maturity-onset diabetes of the young, type 1 10.1
42 type 1 diabetes mellitus 10.1
43 hemihyperplasia, isolated 10.1
44 helix syndrome 10.1
45 hypertrophic cardiomyopathy 10.1
46 exocrine pancreatic insufficiency 10.1
47 cerebral palsy 10.1
48 seizure disorder 10.1
49 enterocolitis 10.0
50 insulin-like growth factor i 10.0

Graphical network of the top 20 diseases related to Hyperinsulinemic Hypoglycemia, Familial, 4:



Diseases related to Hyperinsulinemic Hypoglycemia, Familial, 4

Symptoms & Phenotypes for Hyperinsulinemic Hypoglycemia, Familial, 4

Human phenotypes related to Hyperinsulinemic Hypoglycemia, Familial, 4:

31 58 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 decreased 3-hydroxyacyl-coa dehydrogenase level 31 obligate (100%) HP:0100950
2 neonatal hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001319
3 vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002013
4 intrauterine growth retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001511
5 hepatic steatosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0001397
6 elevated hepatic transaminase 58 31 hallmark (90%) Very frequent (99-80%) HP:0002910
7 lethargy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001254
8 neonatal hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001998
9 diarrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0002014
10 confusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0001289
11 proportionate short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0003508
12 fasting hyperinsulinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0008283
13 hyperinsulinemic hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000825
14 hypoketotic hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001985
15 hypoglycemic seizures 58 31 hallmark (90%) Very frequent (99-80%) HP:0002173
16 increased circulating free fatty acid level 58 31 hallmark (90%) Very frequent (99-80%) HP:0030781
17 dicarboxylic aciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003215
18 hypoglycemic encephalopathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0006929
19 increased c-peptide level 58 31 hallmark (90%) Very frequent (99-80%) HP:0030796
20 abnormal circulating acetylcarnitine concentration 31 hallmark (90%) HP:0012071
21 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
22 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
23 motor delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001270
24 peripheral neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0009830
25 hyperammonemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001987
26 prolonged prothrombin time 58 31 occasional (7.5%) Occasional (29-5%) HP:0008151
27 lactic acidosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0003128
28 mildly elevated creatine kinase 58 31 occasional (7.5%) Occasional (29-5%) HP:0008180
29 pigmentary retinopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000580
30 decreased plasma carnitine 58 31 occasional (7.5%) Occasional (29-5%) HP:0003234
31 prolonged qt interval 58 31 very rare (1%) Very rare (<4-1%) HP:0001657
32 hypertrophic cardiomyopathy 58 31 very rare (1%) Very rare (<4-1%) HP:0001639
33 dilated cardiomyopathy 58 31 very rare (1%) Very rare (<4-1%) HP:0001644
34 acute hepatic failure 58 31 very rare (1%) Very rare (<4-1%) HP:0006554
35 hepatic necrosis 58 31 very rare (1%) Very rare (<4-1%) HP:0002605
36 myoglobinuria 58 31 very rare (1%) Very rare (<4-1%) HP:0002913
37 intellectual disability 31 HP:0001249
38 hypoglycemic coma 31 HP:0001325
39 decreased activity of 3-hydroxyacyl-coa dehydrogenase 58 Obligate (100%)
40 abnormality of acetylcarnitine metabolism 58 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Laboratory Abnormalities:
hypoglycemia
hyperinsulinemia
elevated blood spot hydroxybutyryl carnitine

Neurologic Central Nervous System:
seizures, hypoglycemic
mental retardation due to repeated episodes of hypoglycemia
coma, hypoglycemic

Endocrine Features:
hyperinsulinemic hypoglycemia

Clinical features from OMIM®:

609975 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Hyperinsulinemic Hypoglycemia, Familial, 4 according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-116 9.36 AURKB
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-122 9.36 AURKB
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-13 9.36 AURKB
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-144 9.36 DHX30
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 9.36 DHX30
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-177 9.36 DHX30
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-206 9.36 DHX30
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.36 INSR
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.36 DHX30
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.36 DHX30
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-68 9.36 INSR

Drugs & Therapeutics for Hyperinsulinemic Hypoglycemia, Familial, 4

Drugs for Hyperinsulinemic Hypoglycemia, Familial, 4 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 39)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
lanreotide Approved Phase 4 108736-35-2
2 Angiopeptin Phase 4
3
Furosemide Approved, Vet_approved Phase 3 54-31-9 3440
4
Glucagon Approved Phase 3 16941-32-5
5 Sodium Potassium Chloride Symporter Inhibitors Phase 3
6 Radiopharmaceuticals Phase 3
7 diuretics Phase 3
8
Pancrelipase Approved, Investigational Phase 2 53608-75-6
9
Diazoxide Approved Phase 2 364-98-7 3019
10
Levodopa Approved Phase 2 59-92-7 6047
11
Benzocaine Approved, Investigational Phase 1, Phase 2 1994-09-7, 94-09-7 2337
12
tannic acid Approved Phase 1, Phase 2 1401-55-4
13 Gastrointestinal Agents Phase 2
14 pancreatin Phase 2
15 Antineoplastic Agents, Hormonal Phase 2
16 Glucagon-Like Peptide 1 Phase 2
17
Exenatide Approved, Investigational Phase 1 141758-74-9 15991534
18
Acarbose Approved, Investigational Phase 1 56180-94-0 441184
19
Octreotide Approved, Investigational Phase 1 83150-76-9 383414 6400441
20
Somatostatin Approved, Investigational Phase 1 51110-01-1, 38916-34-6 53481605
21
Lactitol Approved, Investigational Phase 1 585-86-4 157355
22 Anti-Obesity Agents Phase 1
23 Cardiac Glycosides Phase 1
24 Glycoside Hydrolase Inhibitors Phase 1
25 Incretins Phase 1
26 insulin Phase 1
27 Insulin, Globin Zinc Phase 1
28
Insulin aspart Approved 116094-23-6 16132418
29
Canagliflozin Approved 842133-18-0
30
Diazepam Approved, Illicit, Investigational, Vet_approved 439-14-5 3016
31
Dopamine Approved 51-61-6, 62-31-7 681
32
gastric inhibitory polypeptide Investigational 100040-31-1
33 Hypoglycemic Agents
34 Sodium-Glucose Transporter 2 Inhibitors
35 Nutrients
36 Dihydroxyphenylalanine
37 Dopamine Agents
38 Neurotransmitter Agents
39 Fluorides

Interventional clinical trials:

(show all 39)
# Name Status NCT ID Phase Drugs
1 Treatment With Lanreotide Autogel (Somatostatin Analogue) in Patients With Congenital Hyperinsulinism of Infancy Already Treated With Somatostatin Analog by Pump Unknown status NCT01070758 Phase 4 Lanreotide autogel
2 A Two-Period, Open-label Trial Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism Completed NCT03777176 Phase 3 dasiglucagon
3 A Randomized Trial in 2 Parts: Double-Blind, Placebo-Controlled, Crossover Part 1 and Open-label Part 2, Evaluating the Efficacy and Safety of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism Recruiting NCT04172441 Phase 2, Phase 3 dasiglucagon;Placebo
4 18F-DOPA II - PET Imaging Optimization Recruiting NCT04706910 Phase 3 18F-DOPA;Furosemide Injection
5 18F-DOPA PET Imaging: an Evaluation of Biodistribution and Safety Active, not recruiting NCT03042416 Phase 3 18F-DOPA
6 An Extension Trial Evaluating the Long-term Safety and Efficacy of Dasiglucagon for the Treatment of Children With Congenital Hyperinsulinism Enrolling by invitation NCT03941236 Phase 3 dasiglucagon
7 A Single-Dose Open-Label Study of XOMA 358 in Subjects With Congenital Hyperinsulinism (HI) Completed NCT02604485 Phase 2 Cohort 1;Cohort 2;Cohort 3;Cohort 4
8 An Open Label Pilot Study of the Effects of the Glucagon-like Peptide-1 Receptor Antagonist, Exendin-(9-39) on Glycemic Control in Subjects With Congenital Hyperinsulinism Completed NCT00571324 Phase 1, Phase 2 Exendin-(9-39)
9 A Phase 2 Proof-of-Concept Study of CSI-Glucagon™ (Continuous Subcutaneous Glucagon Infusion) to Prevent Hypoglycemia With Lower Intravenous Glucose Infusion Rates in Children up to One Year of Age With Congenital Hyperinsulinism Completed NCT02937558 Phase 2 Glucagon
10 A Phase II Safety and Efficacy Study of 18F-L-Fluoro-DOPA PET/CT Scan Localization of Focal Pancreatic Lesions in Children With Hyperinsulinemic Hypoglycemia Completed NCT01468454 Phase 2 18 F-DOPA
11 Localization of Focal Forms of Hyperinsulinism of Infancy With 18F-labeled L-fluoro-DOPA PET Scan Completed NCT00674440 Phase 2 F-DOPA
12 Role of GLP-1 in Congenital Hyperinsulinism:Effect of Exendin-(9-39) on Fasting Adaptation and Protein Sensitivity Completed NCT00897676 Phase 1, Phase 2 Exendin-(9-39);placebo
13 Replace Sandostatine® in Three Daily Subcutaneous Injections by a Single Intramuscular Injection of Sandostatine® LP Per Month in Patients With a Diffuse Form of Hyperinsulinism Completed NCT00987168 Phase 2 Sandostatine LP
14 A Phase 2, Interventional, Randomized, Double-Blind, Placebo-Controlled Pilot Study of Glucagon RTU in Subjects Who Experience Hyperinsulinemic Hypoglycemia After Bariatric Surgery Completed NCT03770637 Phase 2 Glucagon RTU
15 Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass Completed NCT03984370 Phase 2 ZP4207
16 18F-Fluoro-L- DOPA PET Imaging for the Detection and Localization of Focal Congenital Hyperinsulinism Recruiting NCT04205604 Phase 2 18F-Fluoro Dopa Imaging
17 An Open-Label Multiple-Dose Study of RZ358 in Patients With Congenital Hyperinsulinism Recruiting NCT04538989 Phase 2 RZ358 Sequential Group Cohort 1;RZ358 Sequential Group Cohort 2;RZ358 Sequential Group Cohort 3;RZ358 Sequential Group Cohort 4
18 A Phase 2, Multiple Ascending Dose, Open-label, Proof-of-concept Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of HM15136 Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI) Not yet recruiting NCT04732416 Phase 2 HM15136
19 A Phase 2, Open-Label, Cross-over Study to Assess the Safety and Efficacy of Avexitide in Acquired Hyperinsulinemic Hypoglycemia Not yet recruiting NCT04652479 Phase 2 Avexitide
20 Role of Glucagon-Like Peptide-1 (GLP-1) in Congenital Hyperinsulinism: Effect of Exendin (9-39) on Glucose Requirements to Maintain Euglycemia Terminated NCT00835328 Phase 1, Phase 2 Exendin (9-39);Vehicle
21 Pilot Study of the Efficacy and Safety of Sirolimus in the Treatment of Congenital Hyperinsulinism. Withdrawn NCT02524639 Phase 1, Phase 2 Sirolimus
22 Pasireotide for Prevention of Hypoglycemia in Patients With Hyperinsulinemic Hypoglycemia Withdrawn NCT03053284 Phase 2 Pasireotide 0.6Mg Solution for Injection;Saline Solution
23 A Pilot Study Evaluating Exenatide for the Treatment of Postprandial Hyperinsulinemic Hypoglycemia Post-RYGB Completed NCT02685852 Phase 1 Exenatide;Acarbose;Placebo
24 The Use of Fluorodopa F 18 Positron Emission Tomography Combined With Computed Tomography in Congenital Hyperinsulinism and Insulinoma Recruiting NCT02021604 Phase 1 Fluorodopa F 18
25 Treatment Plan for an Individual Patient With Pasireotide for Hyperinsulinemic Hypoglycemia Recruiting NCT03103009 Phase 1 Pasireotide
26 Long Term Glucose Metabolism in Conservatively Treated Patients With Congenital Hyperinsulinism Unknown status NCT01819584
27 The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology Unknown status NCT03768518
28 Application of Raw Corn Starch on Patients With Unoperated Insulinoma is Helpful to Decrease Risk of Hypoglycemia Unknown status NCT03930368
29 Towards Individualized Surgery in Non-focal Congenital Hyperinsulinism Completed NCT02108730
30 Bihormonal Bionic Pancreas for the Treatment of Diabetes Post-Pancreatectomy in Children With Congenital Hyperinsulinism - A Pilot Study Completed NCT03303196
31 Prevention of Hypoglycemia in Patients With Post-Gastric Bypass Hyperinsulinemic Hypoglycemia Completed NCT01933490
32 Deciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia After Bariatric Surgery, Part 1 C: Effect of Postprandial Hypoglycaemia on Driving Performance. Completed NCT04330196
33 New Imaging Procedure for the Localisation of Insulinoma Completed NCT02127541
34 Deciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia After Bariatric Surgery Part 1 B: Evaluation of the Neuro-endocrine Response to Hypoglycaemia. Recruiting NCT04334161
35 Canagliflozin: a New Therapeutic Option in Patients That Present Postprandial Hyperinsulinemic Hypoglycemia After Roux-en-Y-gastric By-pass Recruiting NCT04720859 Canagliflozin 300 MG Oral Tablet
36 Role of Nutrient Transit and Incretin Hormones in Hyperinsulinemic Hypoglycemia Recruiting NCT04615546
37 Compassionate Use of SOM230 for Individual Patient (NS, 14-Jan-1986) With Hyperinsulinemic/Hypoglycemia Available NCT02835131 Pasireotide
38 Expanded Access Use of 18F-L-Fluoro-DOPA PET/CT Scan Localization of Focal Pancreatic Lesions in Subjects With Hyperinsulinemic Hypoglycemia Available NCT01916148 18F-DOPA
39 Phase II Study of the Use of [18F]-DOPA in Hyperinsulinemic Hypoglycemia No longer available NCT02533219 18 F-DOPA

Search NIH Clinical Center for Hyperinsulinemic Hypoglycemia, Familial, 4

Genetic Tests for Hyperinsulinemic Hypoglycemia, Familial, 4

Genetic tests related to Hyperinsulinemic Hypoglycemia, Familial, 4:

# Genetic test Affiliating Genes
1 Hyperinsulinemic Hypoglycemia, Familial, 4 29 HADH

Anatomical Context for Hyperinsulinemic Hypoglycemia, Familial, 4

MalaCards organs/tissues related to Hyperinsulinemic Hypoglycemia, Familial, 4:

40
Pancreas, Kidney, Pituitary, Spleen, Brain

Publications for Hyperinsulinemic Hypoglycemia, Familial, 4

Articles related to Hyperinsulinemic Hypoglycemia, Familial, 4:

(show top 50) (show all 607)
# Title Authors PMID Year
1
Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation. 57 6 61
14693719 2004
2
Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation. 57 6
23273570 2013
3
Genome-wide homozygosity analysis reveals HADH mutations as a common cause of diazoxide-responsive hyperinsulinemic-hypoglycemia in consanguineous pedigrees. 57 6
21252247 2011
4
Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. 6 57
11489939 2001
5
Glucagon deficiency causing severe neonatal hypoglycemia in a patient with normal insulin secretion. 6 57
904979 1977
6
Identification of a diffuse form of hyperinsulinemic hypoglycemia by 18-fluoro-L-3,4 dihydroxyphenylalanine positron emission tomography/CT in a patient carrying a novel mutation of the HADH gene. 6 61
19318379 2009
7
Sequencing analysis of insulin receptor defects and detection of two novel mutations in INSR gene. 6
27896077 2014
8
A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene. 6
15161766 2004
9
Hunting for a hypoglycemia gene: severe neonatal hypoglycemia in a consanguineous family. 57
12400064 2002
10
Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance. 6
8288049 1994
11
Biphasic dynamics of beta cell mass in a mouse model of congenital hyperinsulinism: implications for type 2 diabetes. 61
33558985 2021
12
Congenital Hyperinsulinism. 61
33795398 2021
13
Focal congenital hyperinsulinism resulting from biallelic loss of function of KCNJ11 gene. 61
33762279 2021
14
SUR1-mutant iPS cell-derived islets recapitulate the pathophysiology of congenital hyperinsulinism. 61
33404684 2021
15
Clinical and genetic characteristics of patients with congenital hyperinsulinism in 21 non-consanguineous families from Serbia. 61
33770274 2021
16
Long-Term Outcome and Treatment in Persistent and Transient Congenital Hyperinsulinism: A Finnish Population-Based Study. 61
33475139 2021
17
Intraoperative ultrasound imaging in the surgical treatment of congenital hyperinsulinism: prospective, blinded study. 61
33688939 2021
18
Marked clinical heterogeneity in congenital hyperinsulinism due to a novel homozygous ABCC8 mutation. 61
33595839 2021
19
Clinical characteristics, outcome, and predictors of neurological sequelae of persistent congenital hyperinsulinism: A single tertiary center experience. 61
33528087 2021
20
Sirolimus Therapy and Follow-up in a Patient with Severe Congenital Hyperinsulinism Following Subtotal Pancreatectomy 61
32482020 2021
21
A Novel Homozygous Missense Mutation in the YARS Gene: Expanding the Phenotype of YARS Multisystem Disease. 61
33490854 2021
22
Functional characterization of ABCC8 variants of unknown significance based on bioinformatics predictions, splicing assays, and protein analyses: Benefits for the accurate diagnosis of congenital hyperinsulinism. 61
33410562 2021
23
Functional evaluation of 16 SCHAD missense variants: Only amino acid substitutions causing congenital hyperinsulinism of infancy lead to loss-of-function phenotypes in vitro. 61
32876354 2021
24
Gut Microbiome Profile After Pancreatectomy in Infants With Congenital Hyperinsulinism. 61
33370028 2021
25
A de novo CACNA1D missense mutation in a patient with congenital hyperinsulinism, primary hyperaldosteronism and hypotonia. 61
32336187 2020
26
Open-Source Technology for Real-Time Continuous Glucose Monitoring in the Neonatal Intensive Care Unit: Case Study in a Neonate With Transient Congenital Hyperinsulinism. 61
33275114 2020
27
Receptor-Targeted Photodynamic Therapy of Glucagon-Like Peptide 1 Receptor-Positive Lesions. 61
32385165 2020
28
Aberrant methylation underlies insulin gene expression in human insulinoma. 61
33060578 2020
29
[The use of long-acting somatostatin analogs in congenital hyperinsulinism]. 61
33369374 2020
30
[Congenital hyperinsulinism in Gran Canaria, Canary Isles]. 61
33082084 2020
31
Long-term Follow-up of Patients with Congenital Hyperinsulinism in Austria. 61
33600688 2020
32
Detection of hepatocyte nuclear factor 4A(HNF4A) gene variant as the cause for congenital hyperinsulinism leads to revision of the diagnosis of the mother. 61
33031054 2020
33
Diagnosis of congenital Hyperinsulinism can occur not only in infancy but also in later age: a new flow chart from a single center experience. 61
32928245 2020
34
[Continuous subcutaneous infusion of somatostatin analogues in the treatment of congenital hyperinsulinism]. 61
33351342 2020
35
Suspected congenital hyperinsulinism in a Shiba Inu dog. 61
32592436 2020
36
The role of 18F-DOPA PET/CT in the diagnosis of the congenital focal form of hyperinsulinism in children. 61
32448747 2020
37
[Congenital hyperinsulinism in three patients from the same family. Expanding the genotype of this disease]. 61
32819847 2020
38
Focal form of congenital hyperinsulinism in a newborn diagnosed with 18F-DOPA PET/CT allows laparoscopic surgical approach. 61
32800749 2020
39
Challenges of managing congenital hyperinsulinism in remote Aboriginal Australian communities. 61
32808382 2020
40
A Rare Cause of Hyperinsulinemic Hypoglycemia: Kabuki Syndrome 61
32830475 2020
41
Congenital Hyperinsulinism: Two case reports with different rare variants in ABCC8. 61
32871644 2020
42
Mutations in PMM2 gene in four unrelated Spanish families with polycystic kidney disease and hyperinsulinemic hypoglycemia. 61
32841164 2020
43
Octreotide-related exocrine pancreatic insufficiency (EPI) in congenital hyperinsulinism. 61
32634108 2020
44
Inheritance of a paternal ABCC8 variant and maternal loss of heterozygosity at 11p15 retrospectively unmasks the etiology in a case of Congenital hyperinsulinism. 61
32695361 2020
45
Persistent Hypoglycemia in Seven-year-old Saudi Child: A Case Report. 61
32802414 2020
46
Detection of Insulinomas Using Dual-Time-Point 68Ga-DOTA-Exendin 4 PET/CT. 61
32453080 2020
47
18-F-L 3,4-Dihydroxyphenylalanine PET/Computed Tomography in the Management of Congenital Hyperinsulinism. 61
32498990 2020
48
Multiplexing DNA methylation markers to detect circulating cell-free DNA derived from human pancreatic β cells. 61
32573495 2020
49
Targeted Optical Imaging of the Glucagonlike Peptide 1 Receptor Using Exendin-4-IRDye 800CW. 61
31924726 2020
50
Cardiopulmonary Bypass for a Patient With Congenital Hyperinsulinemia. 61
29334830 2020

Variations for Hyperinsulinemic Hypoglycemia, Familial, 4

ClinVar genetic disease variations for Hyperinsulinemic Hypoglycemia, Familial, 4:

6 (show top 50) (show all 131)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HADH NM_005327.5(HADH):c.118G>A (p.Ala40Thr) SNV Pathogenic 8018 rs137853101 GRCh37: 4:108911206-108911206
GRCh38: 4:107990050-107990050
2 HADH NM_005327.5(HADH):c.171C>A (p.Asp57Glu) SNV Pathogenic 8019 rs137853102 GRCh37: 4:108930953-108930953
GRCh38: 4:108009797-108009797
3 INSR NM_000208.4(INSR):c.1610+2T>C SNV Pathogenic 211189 rs797045624 GRCh37: 19:7167977-7167977
GRCh38: 19:7167966-7167966
4 INSR NM_000208.4(INSR):c.3602G>A (p.Arg1201Gln) SNV Pathogenic 14708 rs121913156 GRCh37: 19:7120688-7120688
GRCh38: 19:7120677-7120677
5 HADH NM_005327.7(HADH):c.261+1G>A SNV Pathogenic 802082 rs1398546361 GRCh37: 4:108931044-108931044
GRCh38: 4:108009888-108009888
6 HADH NM_005327.7(HADH):c.587del (p.Ser196fs) Deletion Pathogenic 802083 rs745727504 GRCh37: 4:108944670-108944670
GRCh38: 4:108023514-108023514
7 HADH NM_005327.5(HADH):c.773C>T (p.Pro258Leu) SNV Pathogenic 8020 rs137853103 GRCh37: 4:108954395-108954395
GRCh38: 4:108033239-108033239
8 HADH HADH, 6-BP DEL Deletion Pathogenic 8021 GRCh37:
GRCh38:
9 HADH NM_005327.5(HADH):c.706C>T (p.Arg236Ter) SNV Pathogenic 39482 rs375717077 GRCh37: 4:108948913-108948913
GRCh38: 4:108027757-108027757
10 HADH HADH, EX1DEL Deletion Pathogenic 39483 GRCh37:
GRCh38:
11 HADH NM_005327.5(HADH):c.636+471G>T SNV Pathogenic 39484 rs786200932 GRCh37: 4:108945190-108945190
GRCh38: 4:108024034-108024034
12 HADH NM_005327.7(HADH):c.710-822C>A SNV Pathogenic 1028360 GRCh37: 4:108953510-108953510
GRCh38: 4:108032354-108032354
13 HADH NM_005327.5(HADH):c.676T>C (p.Tyr226His) SNV Conflicting interpretations of pathogenicity 212734 rs146036912 GRCh37: 4:108948883-108948883
GRCh38: 4:108027727-108027727
14 HADH NM_005327.5(HADH):c.456G>T (p.Gln152His) SNV Conflicting interpretations of pathogenicity 211127 rs1051519 GRCh37: 4:108940732-108940732
GRCh38: 4:108019576-108019576
15 HADH NM_005327.5(HADH):c.643C>A (p.Pro215Thr) SNV Conflicting interpretations of pathogenicity 549514 rs140413151 GRCh37: 4:108948850-108948850
GRCh38: 4:108027694-108027694
16 HADH NM_005327.7(HADH):c.*514A>G SNV Uncertain significance 900590 GRCh37: 4:108956027-108956027
GRCh38: 4:108034871-108034871
17 HADH NM_005327.7(HADH):c.688G>A (p.Ala230Thr) SNV Uncertain significance 900535 GRCh37: 4:108948895-108948895
GRCh38: 4:108027739-108027739
18 HADH NM_005327.7(HADH):c.688G>A (p.Ala230Thr) SNV Uncertain significance 900535 GRCh37: 4:108948895-108948895
GRCh38: 4:108027739-108027739
19 HADH NM_005327.7(HADH):c.710-14C>T SNV Uncertain significance 900536 GRCh37: 4:108954318-108954318
GRCh38: 4:108033162-108033162
20 HADH NM_005327.7(HADH):c.710-14C>T SNV Uncertain significance 900536 GRCh37: 4:108954318-108954318
GRCh38: 4:108033162-108033162
21 HADH NM_005327.7(HADH):c.*383G>C SNV Uncertain significance 900589 GRCh37: 4:108955896-108955896
GRCh38: 4:108034740-108034740
22 HADH NC_000004.12:g.107989730A>G SNV Uncertain significance 902091 GRCh37: 4:108910886-108910886
GRCh38: 4:107989730-107989730
23 HADH NC_000004.12:g.107989730A>G SNV Uncertain significance 902091 GRCh37: 4:108910886-108910886
GRCh38: 4:107989730-107989730
24 HADH NM_005327.7(HADH):c.132+6C>G SNV Uncertain significance 902147 GRCh37: 4:108911226-108911226
GRCh38: 4:107990070-107990070
25 HADH NM_005327.7(HADH):c.132+6C>G SNV Uncertain significance 902147 GRCh37: 4:108911226-108911226
GRCh38: 4:107990070-107990070
26 HADH NM_005327.5(HADH):c.132+7G>T SNV Uncertain significance 211125 rs534966818 GRCh37: 4:108911227-108911227
GRCh38: 4:107990071-107990071
27 HADH NM_005327.5(HADH):c.132+7G>T SNV Uncertain significance 211125 rs534966818 GRCh37: 4:108911227-108911227
GRCh38: 4:107990071-107990071
28 HADH NM_005327.7(HADH):c.863A>C (p.Gln288Pro) SNV Uncertain significance 1060607 GRCh37: 4:108955431-108955431
GRCh38: 4:108034275-108034275
29 HADH NM_005327.5(HADH):c.275T>G (p.Phe92Cys) SNV Uncertain significance 211126 rs61735992 GRCh37: 4:108935600-108935600
GRCh38: 4:108014444-108014444
30 HADH NM_005327.5(HADH):c.349G>C (p.Val117Leu) SNV Uncertain significance 652881 rs146732064 GRCh37: 4:108935674-108935674
GRCh38: 4:108014518-108014518
31 HADH NM_005327.5(HADH):c.456G>T (p.Gln152His) SNV Uncertain significance 211127 rs1051519 GRCh37: 4:108940732-108940732
GRCh38: 4:108019576-108019576
32 HADH NM_005327.7(HADH):c.*279C>A SNV Uncertain significance 899454 GRCh37: 4:108955792-108955792
GRCh38: 4:108034636-108034636
33 HADH NM_005327.7(HADH):c.*279C>A SNV Uncertain significance 899454 GRCh37: 4:108955792-108955792
GRCh38: 4:108034636-108034636
34 HADH NM_005327.7(HADH):c.*335C>A SNV Uncertain significance 899455 GRCh37: 4:108955848-108955848
GRCh38: 4:108034692-108034692
35 HADH NM_005327.7(HADH):c.*335C>A SNV Uncertain significance 899455 GRCh37: 4:108955848-108955848
GRCh38: 4:108034692-108034692
36 HADH NM_005327.7(HADH):c.*377G>A SNV Uncertain significance 899456 GRCh37: 4:108955890-108955890
GRCh38: 4:108034734-108034734
37 HADH NM_005327.7(HADH):c.*377G>A SNV Uncertain significance 899456 GRCh37: 4:108955890-108955890
GRCh38: 4:108034734-108034734
38 HADH NC_000004.12:g.107989877C>A SNV Uncertain significance 900414 GRCh37: 4:108911033-108911033
GRCh38: 4:107989877-107989877
39 HADH NC_000004.12:g.107989877C>A SNV Uncertain significance 900414 GRCh37: 4:108911033-108911033
GRCh38: 4:107989877-107989877
40 HADH NM_005327.7(HADH):c.-34C>T SNV Uncertain significance 900482 GRCh37: 4:108911055-108911055
GRCh38: 4:107989899-107989899
41 HADH NM_005327.7(HADH):c.-34C>T SNV Uncertain significance 900482 GRCh37: 4:108911055-108911055
GRCh38: 4:107989899-107989899
42 HADH NM_005327.5(HADH):c.643C>A (p.Pro215Thr) SNV Uncertain significance 549514 rs140413151 GRCh37: 4:108948850-108948850
GRCh38: 4:108027694-108027694
43 HADH NM_005327.7(HADH):c.133-15C>T SNV Uncertain significance 902148 GRCh37: 4:108930900-108930900
GRCh38: 4:108009744-108009744
44 HADH NM_005327.7(HADH):c.159A>G (p.Val53=) SNV Uncertain significance 902149 GRCh37: 4:108930941-108930941
GRCh38: 4:108009785-108009785
45 HADH NM_005327.7(HADH):c.159A>G (p.Val53=) SNV Uncertain significance 902149 GRCh37: 4:108930941-108930941
GRCh38: 4:108009785-108009785
46 HADH NM_005327.7(HADH):c.809C>T (p.Thr270Met) SNV Uncertain significance 902197 GRCh37: 4:108954431-108954431
GRCh38: 4:108033275-108033275
47 HADH NM_005327.7(HADH):c.809C>T (p.Thr270Met) SNV Uncertain significance 902197 GRCh37: 4:108954431-108954431
GRCh38: 4:108033275-108033275
48 HADH NM_005327.7(HADH):c.823G>A (p.Asp275Asn) SNV Uncertain significance 902198 GRCh37: 4:108954445-108954445
GRCh38: 4:108033289-108033289
49 HADH NM_005327.7(HADH):c.823G>A (p.Asp275Asn) SNV Uncertain significance 902198 GRCh37: 4:108954445-108954445
GRCh38: 4:108033289-108033289
50 HADH NM_005327.7(HADH):c.825T>G (p.Asp275Glu) SNV Uncertain significance 902199 GRCh37: 4:108954447-108954447
GRCh38: 4:108033291-108033291

UniProtKB/Swiss-Prot genetic disease variations for Hyperinsulinemic Hypoglycemia, Familial, 4:

72
# Symbol AA change Variation ID SNP ID
1 HADH p.Pro258Leu VAR_024081 rs137853103

Expression for Hyperinsulinemic Hypoglycemia, Familial, 4

Search GEO for disease gene expression data for Hyperinsulinemic Hypoglycemia, Familial, 4.

Pathways for Hyperinsulinemic Hypoglycemia, Familial, 4

GO Terms for Hyperinsulinemic Hypoglycemia, Familial, 4

Cellular components related to Hyperinsulinemic Hypoglycemia, Familial, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear membrane GO:0031965 8.8 TMEM97 SCAI HOXA7

Biological processes related to Hyperinsulinemic Hypoglycemia, Familial, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 learning GO:0007612 8.62 INSR ELAVL4

Sources for Hyperinsulinemic Hypoglycemia, Familial, 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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29 GTR
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56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
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