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LEPD
MCID: LPT014
MIFTS: 74

Leptin Deficiency or Dysfunction (LEPD)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases, Reproductive diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
Sources

Aliases & Classifications for Leptin Deficiency or Dysfunction

About this section

MalaCards integrated aliases for Leptin Deficiency or Dysfunction:

Name: Leptin Deficiency or Dysfunction 56 12 52 73 29 6 71
Obesity Due to Congenital Leptin Deficiency 12 52 25 58 73
Morbid Obesity 12 29 6 15 17
Lepd 56 12 52 25 73
Obesity, Morbid, Due to Leptin Deficiency 56 25 13
Congenital Leptin Deficiency 12 25 15
Leptin Deficiency 25 73 36
Obesity, Severe, Due to Leptin Deficiency 25 39
Obesity, Morbid, Nonsyndromic 1 52 25
Obesity, Morbid 56 43
Severe Obesity 12 15
Morbid Obesity Due to Leptin Deficiency 73
Non-Syndromic Morbid Obesity 1 73
Leptin Dysfunction 6
Obesity Morbid 54
Leptin 17

Characteristics:

Orphanet epidemiological data:

58
obesity due to congenital leptin deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
some patients have a secreted but biologically inactive mutant leptin
hyperphagia and weight gain as well as immunologic abnormalities and hypogonadism can be reversed by exogenously administered recombinant leptin
patients do not exhibit risk factors for cardiovascular disease such as hypertension, lipid dysregulation, or hyperglycemia
immune and endocrine function may improve in some adult patients


HPO:

31
leptin deficiency or dysfunction:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Metabolic diseases
Anatomical: Reproductive diseases Endocrine diseases Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare infertility disorders
Rare gynaecological and obstetric diseases
Rare endocrine diseases


Sources

Summaries for Leptin Deficiency or Dysfunction

About this section
NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 66628 Definition Congenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia. Epidemiology It has been described in less than 30 patients. Clinical description Patients with congenital leptin deficiency are severely hyperphagic from early infancy and, although birthweight is normal, they rapidly become obese during early childhood. An increased susceptibility to infections has also been reported in these infants and appears to be associated with reduced numbers of circulating CD4+ T cells , and impaired T cell proliferation and cytokine release. Other features of the disorder include hyperinsulinaemia, advanced bone age, hypothalamic hypothyroidism and hypogonadotropic hypogonadism leading to a failure to undergo puberty. Etiology Leptin is an adipocyte-derived hormone that plays an important role in energy balance and appetite suppression. Whilst the majority of obese patients display hyperleptinaemia, patients with congenital leptin deficiency have undetectable levels of leptin in the serum. This absence of serum leptin is caused by homozygous frameshift or missense mutations in the ob gene (7q31.3) and is inherited as an autosomal recessive trait . However, a similar phenotype has been observed in three individuals from one consanguineous family who carried homozygous mutations in the gene encoding the leptin receptor (LEPR , 1p31). Diagnostic methods Family history , severe hyperphagia and early-onset obesity may lead to suspicion of a monogenic obesity syndrome . The diagnosis of congenital leptin deficiency can be confirmed by analysis of serum leptin levels or identification of mutations in the ob gene. Management and treatment Congenital leptin deficiency can be successfully treated with daily subcutaneous injections of recombinant human leptin, resulting in sustained positive effects on weight loss, reducing appetite, appropriate pubertal development and hyperinsulinaemia. Prognosis As a result, the prognosis for patients undergoing treatment appears to be excellent. However, misdiagnosed patients are at risk of developing the complications normally associated with severe obesity (in particular type 2 diabetes), with the prognosis being hampered further by an increased rate of mortality due to childhood infection. Visit the Orphanet disease page for more resources.

MalaCards based summary : Leptin Deficiency or Dysfunction, also known as obesity due to congenital leptin deficiency, is related to congenital generalized lipodystrophy and fatty liver disease, and has symptoms including obesity, metabolically benign An important gene associated with Leptin Deficiency or Dysfunction is LEP (Leptin), and among its related pathways/superpathways are Neuroactive ligand-receptor interaction and Adipocytokine signaling pathway. The drugs Nadroparin and Losartan have been mentioned in the context of this disorder. Affiliated tissues include liver, bone and breast, and related phenotypes are obesity and decreased serum leptin

Disease Ontology : 12 A syndrome characterized by severe early-onset obesity, hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine and metabolic dysfunction that has material basis in homozygous or compound heterozygous mutation in LEP on chromosome 7q32.1.

Genetics Home Reference : 25 Congenital leptin deficiency is a condition that causes severe obesity beginning in the first few months of life. Affected individuals are of normal weight at birth, but they are constantly hungry and quickly gain weight. Without treatment, the extreme hunger continues and leads to chronic excessive eating (hyperphagia) and obesity. Beginning in early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children over food, hoarding food, and eating in secret. People with congenital leptin deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Without treatment, affected individuals experience delayed puberty or do not go through puberty, and may be unable to conceive children (infertile).

OMIM : 56 Leptin deficiency is characterized by severe early-onset obesity, hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic dysfunction (Ozata et al., 1999). (614962)

KEGG : 36 Congenital leptin deficiency is a rare human genetic syndrome resulting in severe hyperphagia and early-onset obesity. Beneficial effects of leptin replacement therapy in this condition has been reported.

UniProtKB/Swiss-Prot : 73 Leptin deficiency: A rare disease characterized by low levels of serum leptin, severe hyperphagia and intractable obesity from an early age.

Sources

Related Diseases for Leptin Deficiency or Dysfunction

About this section

Diseases related to Leptin Deficiency or Dysfunction via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 1151)
# Related Disease Score Top Affiliating Genes
1 congenital generalized lipodystrophy 33.6 PPARG LEP INS
2 fatty liver disease 31.7 RETN PPARG LEPR LEP INS ADIPOQ
3 gastroesophageal reflux 31.7 PYY NPY GHRL GCG CCK ADIPOQ
4 cholelithiasis 31.5 LEP INS CCK
5 non-alcoholic fatty liver disease 31.5 RETN PPARG LPL LEPR LEP INS
6 fatty liver disease, nonalcoholic 1 31.4 RETN LEP INS ADIPOQ
7 dumping syndrome 31.4 PYY INS GHRL GCG CCK
8 osteoporosis 31.4 RETN PPARG LEPR LEP INS GHRL
9 obesity-hypoventilation syndrome 31.3 RETN LEP ADIPOQ
10 lipodystrophy, congenital generalized, type 1 31.2 PPARG LEP INS ADIPOQ
11 apnea, obstructive sleep 31.2 RETN LEP INS HCRT GHRL GCG
12 pain agnosia 31.2 POMC CCK ADRB3
13 liver cirrhosis 31.1 RETN NPY LEPR LEP ADIPOQ
14 berardinelli-seip congenital lipodystrophy 31.1 PPARG LEP
15 mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 31.1 LEP INS ADIPOQ
16 bone resorption disease 31.1 PPARG LEP INS
17 hypoglycemia 31.1 POMC INS GHRL GCG
18 hyperuricemia 31.1 PPARG LEP INS ADRB3
19 pre-eclampsia 31.0 LEPR LEP INS ADRB3 ADIPOQ
20 kidney disease 31.0 RETN PPARG LEP INS GCG ADIPOQ
21 ileus 31.0 POMC INS GHRL CCK
22 familial partial lipodystrophy 31.0 RETN PPARG LEP INS ADIPOQ
23 irritable bowel syndrome 30.9 PYY POMC GHRL CCK
24 coronary heart disease 1 30.9 RETN LPL INS ADIPOQ
25 genetic obesity 30.9 LEPR LEP
26 atherosclerosis susceptibility 30.9 RETN PPARG LPL LEP INS ADIPOQ
27 diarrhea 30.9 PYY POMC LEP CCK
28 familial hyperlipidemia 30.8 PPARG LPL LEP INS ADRB3 ADIPOQ
29 alcohol dependence 30.8 PPARG POMC NPY LEP HCRT GHRL
30 anxiety 30.8 POMC NPY INS HCRT CCK
31 acute pancreatitis 30.8 RETN LPL INS CCK
32 gallbladder disease 30.8 PYY INS CCK
33 acanthosis nigricans 30.8 PPARG LEP INS ADIPOQ
34 pericarditis 30.8 RETN LEP ADIPOQ
35 amenorrhea 30.8 POMC LEP INS GHRL
36 arteriosclerosis 30.8 PPARG LPL INS GHRL ADIPOQ
37 sleep disorder 30.8 POMC LEP INS HCRT GHRL ADIPOQ
38 syndromic obesity 30.8 SIM1 POMC LEPR LEP
39 severe pre-eclampsia 30.7 LEPR LEP ADIPOQ
40 polycystic ovary syndrome 30.7 RETN PPARG POMC LEP INS GHRL
41 wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome 30.7 SIM1 SH2B1 MC4R
42 hyperglycemia 30.7 RETN PYY PPARG LPL LEP INS
43 arteries, anomalies of 30.7 PPARG LEP INS ADIPOQ
44 uremia 30.7 RETN LPL LEP INS
45 hyperlipidemia, familial combined, 3 30.7 LPL LEPR INS ADRB3 ADIPOQ
46 chronic kidney disease 30.7 RETN POMC LPL LEPR LEP INS
47 prediabetes syndrome 30.7 PPARG LEP INS GCG ADIPOQ
48 glucose intolerance 30.7 RETN PPARG POMC NPY LPL LEPR
49 pancreatitis 30.7 LPL INS GCG CCK
50 celiac disease 1 30.7 PYY INS GHRL GCG CCK

Graphical network of the top 20 diseases related to Leptin Deficiency or Dysfunction:



Diseases related to Leptin Deficiency or Dysfunction
Sources

Symptoms & Phenotypes for Leptin Deficiency or Dysfunction

About this section

Human phenotypes related to Leptin Deficiency or Dysfunction:

58 31 (show all 27)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 obesity 58 31 obligate (100%) Obligate (100%) HP:0001513
2 decreased serum leptin 58 31 obligate (100%) Obligate (100%) HP:0003292
3 primary amenorrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0000786
4 hyperinsulinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000842
5 gynecomastia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000771
6 decreased testicular size 58 31 hallmark (90%) Very frequent (99-80%) HP:0008734
7 hypergonadotropic hypogonadism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000815
8 decreased serum estradiol 58 31 hallmark (90%) Very frequent (99-80%) HP:0008214
9 polyphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002591
10 hypoplasia of the ovary 58 31 hallmark (90%) Very frequent (99-80%) HP:0008724
11 absence of secondary sex characteristics 58 31 hallmark (90%) Very frequent (99-80%) HP:0008187
12 decreased t cell activation 58 31 hallmark (90%) Very frequent (99-80%) HP:0005419
13 decreased serum testosterone level 31 hallmark (90%) HP:0040171
14 decreased proportion of cd4-positive helper t cells 31 hallmark (90%) HP:0005407
15 hypertriglyceridemia 58 31 frequent (33%) Frequent (79-30%) HP:0002155
16 recurrent upper respiratory tract infections 58 31 frequent (33%) Frequent (79-30%) HP:0002788
17 accelerated skeletal maturation 58 31 frequent (33%) Frequent (79-30%) HP:0005616
18 orthostatic hypotension due to autonomic dysfunction 58 31 frequent (33%) Frequent (79-30%) HP:0004926
19 pituitary hypothyroidism 58 31 frequent (33%) Frequent (79-30%) HP:0008245
20 insulin-resistant diabetes mellitus 58 31 frequent (33%) Frequent (79-30%) HP:0000831
21 micropenis 31 HP:0000054
22 recurrent pneumonia 31 HP:0006532
23 hypogonadism 31 HP:0000135
24 decreased testosterone in males 58 Very frequent (99-80%)
25 decreased proportion of cd4-positive t cells 58 Very frequent (99-80%)
26 abnormal eating behavior 31 HP:0100738
27 recurrent ear infections 31 HP:0410018

Symptoms via clinical synopsis from OMIM:

56
Genitourinary Internal Genitalia Female:
primary amenorrhea
small ovaries

Genitourinary:
hypogonadism

Growth Weight:
normal birth weight
early-onset severe obesity

Genitourinary Internal Genitalia Male:
small testes

Abdomen Gastrointestinal:
hyperphagia

Respiratory Lung:
recurrent pulmonary infections

Skin Nails Hair Hair:
no beard
sparse pubic and axillary hair

Immunology:
frequent infections in childhood
reduced number of ct4+ t cells (in some patients)
increase in cd8+ t cells (in some patients)
increase in b cells (in some patients)
marked reduction in cd4+/cd8+ ratio (in some patients)
more
Chest Breasts:
gynecomastia

Head And Neck Ears:
recurrent ear infections

Genitourinary External Genitalia Male:
small penis

Endocrine Features:
low testosterone levels
low estradiol levels
low serum leptin levels (in most patients)
high serum leptin levels (rare)
hypothalamic hypogonadism
more
Neurologic Behavioral Psychiatric Manifestations:
hyperphagia

Respiratory Nasopharynx:
frequent upper respiratory tract infections

Neurologic Peripheral Nervous System:
sympathetic system dysfunction

Clinical features from OMIM:

614962

UMLS symptoms related to Leptin Deficiency or Dysfunction:


obesity, metabolically benign

GenomeRNAi Phenotypes related to Leptin Deficiency or Dysfunction according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00221-A-1 9.75 PPARG
2 Decreased viability GR00221-A-2 9.75 PPARG
3 Decreased viability GR00221-A-3 9.75 PPARG
4 Decreased viability GR00221-A-4 9.75 PPARG
5 Decreased viability GR00240-S-1 9.75 MC3R
6 Decreased viability GR00249-S 9.75 ADRB3 GCG GHRL MC4R SH2B1
7 Decreased viability GR00381-A-1 9.75 ADRB3 MC3R PYY
8 Decreased viability GR00381-A-3 9.75 MC3R
9 Decreased viability GR00386-A-1 9.75 CCK GCG LPL MC3R POMC PPARG
10 Decreased viability GR00402-S-2 9.75 HCRT MC3R MC4R NPY PYY RETN

MGI Mouse Phenotypes related to Leptin Deficiency or Dysfunction:

45 (show all 11)
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 10.4 ADIPOQ ADRB3 AGRP GHRL INS LEP
2 homeostasis/metabolism MP:0005376 10.38 ADIPOQ ADRB3 AGRP CCK GHRL HCRT
3 behavior/neurological MP:0005386 10.35 ADIPOQ ADRB3 AGRP GHRL HCRT INS
4 growth/size/body region MP:0005378 10.34 ADIPOQ ADRB3 AGRP HCRT INS LEP
5 endocrine/exocrine gland MP:0005379 10.2 ADIPOQ ADRB3 CCK GHRL INS LEP
6 nervous system MP:0003631 10.13 ADIPOQ AGRP CCK HCRT INS LEP
7 liver/biliary system MP:0005370 10.11 ADIPOQ AGRP INS LEP LEPR LPL
8 normal MP:0002873 9.81 AGRP GHRL INS LEPR MC4R NPY
9 no phenotypic analysis MP:0003012 9.8 AGRP CCK INS LEPR MC4R POMC
10 renal/urinary system MP:0005367 9.61 ADIPOQ CCK INS LEP LEPR NPY
11 skeleton MP:0005390 9.28 ADIPOQ INS LEP LEPR MC3R MC4R
Sources

Drugs & Therapeutics for Leptin Deficiency or Dysfunction

About this section

Drugs for Leptin Deficiency or Dysfunction (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 583)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nadroparin Approved, Investigational Phase 4
2
Losartan Approved Phase 4 114798-26-4 3961
3
Icodextrin Approved, Investigational Phase 4 337376-15-5
4
Methylprednisolone Approved, Vet_approved Phase 4 83-43-2 6741
5
Prednisolone phosphate Approved, Vet_approved Phase 4 302-25-0
6
Methylprednisolone hemisuccinate Approved Phase 4 2921-57-5
7 Prednisolone acetate Approved, Vet_approved Phase 4 52-21-1
8
Prednisolone Approved, Vet_approved Phase 4 50-24-8 5755
9
Fentanyl Approved, Illicit, Investigational, Vet_approved Phase 4 437-38-7 3345
10
Ketamine Approved, Vet_approved Phase 4 6740-88-1 3821
11
Acetaminophen Approved Phase 4 103-90-2 1983
12
Cefazolin Approved Phase 4 25953-19-9 656510 33255
13
chenodeoxycholic acid Approved Phase 4 474-25-9 10133
14
Ursodeoxycholic acid Approved, Investigational Phase 4 128-13-2 31401
15
Enoxaparin Approved Phase 4 9005-49-6 772
16
Dopamine Approved Phase 4 51-61-6, 62-31-7 681
17
Rocuronium Approved Phase 4 119302-91-9, 143558-00-3 441290
18
Ibuprofen Approved Phase 4 15687-27-1 3672
19
Atorvastatin Approved Phase 4 134523-00-5 60823
20
Bupivacaine Approved, Investigational Phase 4 2180-92-9, 38396-39-3 2474
21
Oxycodone Approved, Illicit, Investigational Phase 4 76-42-6 5284603
22
Methylcobalamin Approved, Investigational Phase 4 13422-55-4
23
Hydroxocobalamin Approved Phase 4 13422-51-0 15589840 11953898
24
Clotrimazole Approved, Vet_approved Phase 4 23593-75-1 2812
25
Miconazole Approved, Investigational, Vet_approved Phase 4 22916-47-8 4189
26
Micafungin Approved, Investigational Phase 4 235114-32-6 477468 3081921
27
Posaconazole Approved, Investigational, Vet_approved Phase 4 171228-49-2 147912
28
Valsartan Approved, Investigational Phase 4 137862-53-4 60846
29
Chlorhexidine Approved, Vet_approved Phase 4 55-56-1 9552079 2713
30
Coal tar Approved Phase 4 8007-45-2
31
Amphotericin B Approved, Investigational Phase 4 1397-89-3 5280965 14956
32
Anidulafungin Approved, Investigational Phase 4 166663-25-8 166548
33
Atropine Approved, Vet_approved Phase 4 51-55-8, 5908-99-6 174174
34
Ketorolac Approved Phase 4 66635-83-4, 74103-06-3 3826
35
Metoclopramide Approved, Investigational Phase 4 364-62-5 4168
36
Anastrozole Approved, Investigational Phase 4 120511-73-1 2187
37
Iron Approved, Experimental Phase 4 15438-31-0, 7439-89-6 27284 23925
38
Pramlintide Approved, Investigational Phase 4 151126-32-8
39
Fenofibrate Approved Phase 4 49562-28-9 3339
40
Ferrous fumarate Approved Phase 4 141-01-5
41
Ferrous gluconate Approved Phase 4 299-29-6
42
Verapamil Approved Phase 4 52-53-9 2520
43
Pioglitazone Approved, Investigational Phase 4 111025-46-8 4829
44
Olanzapine Approved, Investigational Phase 4 132539-06-1 4585
45
Rosiglitazone Approved, Investigational Phase 4 122320-73-4 77999
46
Risperidone Approved, Investigational Phase 4 106266-06-2 5073
47
Aripiprazole Approved, Investigational Phase 4 129722-12-9 60795
48
Promethazine Approved, Investigational Phase 4 60-87-7 4927
49
Diphenhydramine Approved, Investigational Phase 4 58-73-1, 147-24-0 3100
50
Iloperidone Approved Phase 4 133454-47-4 71360

Interventional clinical trials:

(show top 50) (show all 1674)
# Name Status NCT ID Phase Drugs
1 Effect of Bile Acids and Bile Acid Sequstrants on GLP-1 Secretion After Roux-en-Y Gastric Bypass Unknown status NCT02952963 Phase 4 Chenodeoxycholic Acid;Colesevelam
2 Effects of Chenodeoxycholic Acid and Colesevelam on GLP-1 Secretion, During a Meal, After Roux-en-Y Gastric Bypass Unknown status NCT02876484 Phase 4 Colesevelam;Chenodeoxycholic Acid
3 Prospective, Pharmacokinetic Study for Determination of the Relationship Between Lean Body Weight and Anti-Xa Activity 4 Hours After Subcutaneous Injection of 5700 IU Nadroparin in Morbidly Obese Patients After Bariatric Surgery. Unknown status NCT02295150 Phase 4 Nadroparin
4 Correlation of Postoperative VAS Values and Body Mass Index in Patients Undergoing Abdominal Surgery: A Clinical Trial Unknown status NCT02017314 Phase 4 Morphine
5 A Study of the Pharmacokinetics of Dexmedetomidine in Morbid Obesity. Unknown status NCT01864187 Phase 4 Dexmedetomidine
6 International, Multi Centre, Open, Prospective, Randomized Study: Banded Versus Conventional Laparoscopic Roux-en-Y (GABY) Unknown status NCT01015469 Phase 4
7 Prospective Randomized Study of Effects of Laparoscopic Roux-en-Y Gastric Bypass Versus Laparoscopic Sleeve Gastrectomy Unknown status NCT00667706 Phase 4
8 Laparoscopic Bariatric Surgery: Impact of the Level of Neuromuscular Blockade on Surgical Conditions - Comparison Between Moderate and Deep Neuromuscular Blockade Unknown status NCT02118844 Phase 4 rocuronium
9 Evaluation of the Effects of Laying Early (Between 12 and 16) a Gastric Band on the Prevention of Morbid Obesity in Late Adolescence. Randomized Checked Against Standard Management of Obesity in This Population. Unknown status NCT01700738 Phase 4
10 Gut Hormones as Mediators of Different Weight Loss Responses After Roux-en-Y Gastric Bypass Unknown status NCT02374632 Phase 4
11 Laparoscopic Roux-en-Y Gastric Bypass vs. Laparoscopic BPD-Duodenal Switch for Superobesity (BMI > 50 kg/m2)- A Randomized Clinical Trial Unknown status NCT00327912 Phase 4
12 The Need of Dosing Adjustment for Simvastatin in Obese Patients Post Bariatric Surgery- Laparoscopic Sleeve Gastrectomy (LSG) Unknown status NCT03571802 Phase 4 Simvastatin
13 Effects of Non-Glucose-Based Peritoneal Dialysis Solution "EXTRANEAL" on Changes in Leptin Levels and Sympathetic Activity Induced by Conventional Glucose-Based Dialysate "DIANEAL" in Patients on Peritoneal Dialysis Unknown status NCT01228279 Phase 4
14 Ultrasonographic Modification of Liver Steatosis and Visceral Fat Induced by Treatment With Losartan and Simvastatin in Hypertensive Normocholesterolemic Obese Patients Unknown status NCT00669435 Phase 4 Losartan + Simvastatin;Amlodipine + Simvastatin
15 Chronic Metformin Treatment Induces a Dietary Restriction-like State in Overweight Human Unknown status NCT02745886 Phase 4 metformin 0.85 twice daily for 6 months
16 The Employing of the Bio-Hep-B PreS1/PreS2/S Hepatitis B Virus (HBV) Vaccine in New Born Babies From HBV Positive Palestinian Mothers Unknown status NCT01133184 Phase 4
17 The Effect of 6-Methyl-Prednisolone on Organ Dysfunction and Mortality of Patients With Unresolving Multiple Organ Dysfunction Syndrome Unknown status NCT00127985 Phase 4 6-methyl-prednisolone
18 The Impact of Conventional Hemodialysis, High Flux Hemodialysis and Hemodiafiltration on Adiponectin, Vascular Function and Clinical Prognosis Unknown status NCT00155363 Phase 4
19 Endobarrier Treatment in Obese Subjects With T2DM Unknown status NCT01718457 Phase 4
20 Effect of Vitamin D on Metabolic Parameters in Patients With the Metabolic Syndrome Unknown status NCT01237769 Phase 4 Vitamin D3
21 The Therapeutic Effect of Catgut Embedding in Obesity-A Randomized, Double-blind, Placebo-controlled Clinical Trial Unknown status NCT02276235 Phase 4
22 Weight Reduction Alone May Not be Sufficient to Maintain Disease Remission in Obese Patients With Psoriasis: a Randomized, Investigator-blinded Study Unknown status NCT01439425 Phase 4
23 The Monitor of Serum Prolactin Level and Related Clinical Observations Among Individuals With Schizophrenia Spectrum Illnesses in a 3 Months Aripiprazole Trial Unknown status NCT00468533 Phase 4 Aripiprazole
24 A Study on the Efficacy, Pharmacokinetics and Adverse Effects of Paliperidone ER Unknown status NCT02433717 Phase 4 Paliperidone ER
25 The ACT-OUT Trial: ACTivity OUTcomes Based on the Consumption of a High Carbohydrate or High Fat Diet in Patients With Metabolic Syndrome Unknown status NCT01357382 Phase 4
26 Randomized Clinical Trial Between Laparoscopic Gastric Bypass and Laparoscopic Vertical Banded Gastroplasty for Morbid Obesity Completed NCT01639677 Phase 4
27 Pharmacokinetics of Intravenous Acetaminophen and Its Metabolites in Morbidly Obese Patients Completed NCT01764555 Phase 4 acetaminophen 2 g
28 CYP3A4 Metabolism Before and After Surgery Induced Weight Loss in Morbidly Obese Patients Using Midazolam as a Model Drug Completed NCT01519726 Phase 4 Midazolam
29 Effects of Ursodeoxycholic Acid and Chenodeoxycholic Acid on GLP-1 Secretion After Roux-en-Y Gastric Bypass Completed NCT02340247 Phase 4 Ursodeoxycholic Acid;Chenodeoxycholic Acid
30 A Post Implantation/Post Market Evaluation of Safety and Quality of Life in Subjects Implanted With the Swedish Adjustable Gastric Band (SAGB) During Protocol CI-02-0006 Completed NCT00543140 Phase 4
31 Comparisons of iv Ibuprofen and iv Paracetamol for Postoperative Pain Levels and Opioid Consumption During Bariatric Surgery Completed NCT02778958 Phase 4 paracetamol;ibuprofen
32 Investigations on the Influence of Bariatric Surgery on the Metabolism and Absorption of Atorvastatin Completed NCT00331565 Phase 4
33 Vitamin Deficiencies and Suppletion in Morbid Obesity Completed NCT02270749 Phase 4 Hydroxocobalamin;FitForMe vitamin B12
34 Micafungin (Mycamine®) Pharmacokinetics Given as a Single Intravenous Dose to Obese Patients (MICADO). Completed NCT03102658 Phase 4 Micafungin
35 Pharmacokinetics of Posaconazole Given as a Single Intravenous Dose to Obese Subjects: Dosing Obese With Noxafil® Under a Trial (DONUT) Completed NCT03246386 Phase 4 Posaconazole Injection [Noxafil] 300mg;Posaconazole Injection [Noxafil] 400mg
36 Pharmacokinetics (PK) of Propofol in Bariatric (Morbidly Obese) Patients Completed NCT01536002 Phase 4 Propofol
37 A Novel Preoperative Conditioning Therapy in Giant Obese Patients With the Combination of Liraglutide and a Leucine-Based Amino-Acid Infusion and Caloric Restriction Completed NCT02616003 Phase 4 Liraglutide
38 Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function Completed NCT02206256 Phase 4 Omega-3 fatty acid capsules
39 A Prospective Randomized Clinical Trial Evaluating Surgical Conditions During Laparoscopic Bariatric Surgery With Deep Versus Moderate Neuromuscular Blockade Completed NCT02703909 Phase 4 Rocuronium
40 Clinical, Microbial and Biochemistry Evaluation of Obese Individuals Submitted to One-stage Full-mouth Disinfection. A Clinical Control Parallel Study Completed NCT03103204 Phase 4
41 Pharmacokinetics of Liposomal Amphotericin B (AmBisome®) Given Intravenously to Patients Undergoing Bariatric Surgery Completed NCT02320604 Phase 4 Administration of study drug
42 Efficacy and Tolerability of Garcinia Mangostana Extracts in the Management of Weight Loss in Severe Obese Patients Completed NCT02823561 Phase 4
43 Pharmacokinetics of Anidulafungin (Ecalta ®) Given Intravenously as Prophylaxis to Obese Patients With Risk of Invasive Fungal Infection Undergoing Gastric Bypass Surgery. Completed NCT02021123 Phase 4 Anidulafungin 100mg single dose iv
44 Population Pharmacokinetics and Pharmacodynamics of Propofol in the Morbidly Obese Patient Completed NCT00395681 Phase 4 Diprivan
45 Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot) Completed NCT02959853 Phase 4 Anastrazole
46 Increased Cefazolin (Ancef) Dosing for Prophylaxis During Cesarean Delivery in the Obese Population Completed NCT02049944 Phase 4 Cefazolin
47 Use Of Esomeprazole In Postoperative Bariatric Surgery Patients Users And Non-Users Of Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) Completed NCT00608712 Phase 4 Esomeprazole
48 Intravenous Ibuprofen for Laparoscopic Bariatric Surgery Completed NCT01707251 Phase 4 Intravenous Ibuprofen;Saline
49 Suture Granuloma in Body Contouring Surgery Completed NCT00223132 Phase 4
50 Leptin and Ghrelin in ICU Completed NCT02282501 Phase 4

Search NIH Clinical Center for Leptin Deficiency or Dysfunction

Cochrane evidence based reviews: obesity, morbid

Sources

Genetic Tests for Leptin Deficiency or Dysfunction

About this section

Genetic tests related to Leptin Deficiency or Dysfunction:

# Genetic test Affiliating Genes
1 Leptin Deficiency or Dysfunction 29 LEP
2 Morbid Obesity 29
Sources

Anatomical Context for Leptin Deficiency or Dysfunction

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MalaCards organs/tissues related to Leptin Deficiency or Dysfunction:

40
Liver, Bone, Breast, Brain, Kidney, Heart, Endothelial
Sources

Publications for Leptin Deficiency or Dysfunction

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Articles related to Leptin Deficiency or Dysfunction:

(show top 50) (show all 8223)
# Title Authors PMID Year
1
Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. 61 54 6 56
15070752 2004
2
A leptin missense mutation associated with hypogonadism and morbid obesity. 6 61 54 56
9500540 1998
3
Biologically inactive leptin and early-onset extreme obesity. 56 6
25551525 2015
4
Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy. 56 6
15472169 2004
5
Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. 6 56
12393845 2002
6
Congenital leptin deficiency is associated with severe early-onset obesity in humans. 56 6
9202122 1997
7
Leptin replacement alters brain response to food cues in genetically leptin-deficient adults. 56 54 61
17986612 2007
8
Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. 61 54 56
10523015 1999
9
Positional cloning of the mouse obese gene and its human homologue. 61 56 54
7984236 1994
10
Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice. 56
18515422 2008
11
A role for leptin in sustaining lymphopoiesis and myelopoiesis. 56
18250302 2008
12
Leptin regulates striatal regions and human eating behavior. 56
17690262 2007
13
Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. 56
17118991 2007
14
Is leptin an important physiological regulator of CRP? 56
17206122 2007
15
Induction of leptin resistance through direct interaction of C-reactive protein with leptin. 56
16582918 2006
16
Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. 56
12885755 2003
17
Leptin-deficient mice exhibit impaired host defense in Gram-negative pneumonia. 56
11937559 2002
18
Partial leptin deficiency and human adiposity. 56
11689931 2001
19
Weekly subcutaneous pegylated recombinant native human leptin (PEG-OB) administration in obese men. 56
11095423 2000
20
Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. 56
10660043 2000
21
Peroxisome proliferator-activated receptor gamma C161-->T polymorphism and coronary artery disease. 6
10690291 1999
22
Effects of recombinant leptin therapy in a child with congenital leptin deficiency. 56
10486419 1999
23
Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. 6
9753710 1998
24
Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes. 6
9769326 1998
25
Abnormal regulation of the leptin gene in the pathogenesis of obesity. 56
9751754 1998
26
Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance. 56
9177239 1997
27
Correction of obesity and diabetes in genetically obese mice by leptin gene therapy. 56
8962136 1996
28
Effects of the obese gene product on body weight regulation in ob/ob mice. 56
7624776 1995
29
Weight-reducing effects of the plasma protein encoded by the obese gene. 56
7624777 1995
30
Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. 56
7624778 1995
31
Genetics. In search of a satiety factor. 56
7984230 1994
32
Obesity genes: beneficial effects in heterozygous mice. 56
760211 1979
33
Thermogenic defect in pre-obese ob/ob mice. 56
840297 1977
34
Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? 56
13937884 1962
35
Obese, a new mutation in the house mouse. 56
14824537 1950
36
Chemerin correlates with markers for fatty liver in morbidly obese patients and strongly decreases after weight loss induced by bariatric surgery. 61 54
20375212 2010
37
The relationships between IGF-1 and CRP, NO, leptin, and adiponectin during weight loss in the morbidly obese. 61 54
20195789 2010
38
Rates of lipid fluxes in adipose tissue in vivo after a mixed meal in morbid obesity. 61 54
20084071 2010
39
Estradiol and metabolic syndrome in older italian men: The InCHIANTI Study. 54 61
19059904 2010
40
Metabolic syndrome and insulin resistance in subjects with morbid obesity. 61 54
19841991 2010
41
Leptin-signaling pathways and leptin resistance. 54 61
19955780 2010
42
Ala54Thr polymorphism of fatty acid binding protein 2, role on insulin resistance and cardiovascular risk factors in presurgical morbid obesity patients. 54 61
19475463 2009
43
Effects of acute administration of acylated and unacylated ghrelin on glucose and insulin concentrations in morbidly obese subjects without overt diabetes. 54 61
19628651 2009
44
Inflammatory mediators in morbidly obese subjects: associations with glucose abnormalities and changes after oral glucose. 61 54
19542241 2009
45
A novel function of intestinal gluconeogenesis: central signaling in glucose and energy homeostasis. 54 61
19647621 2009
46
[Study of the relationship between adiponectin, interleukin-18, ghrelin and bone mineral density in morbidly obese women after gastric bypass]. 54 61
19883895 2009
47
Rates of glucose uptake in adipose tissue and muscle in vivo after a mixed meal in women with morbid obesity. 61 54
19435828 2009
48
Maternal obesity and markers of inflammation in pregnancy. 54 61
19505831 2009
49
Adipocyte fatty acid-binding protein as a determinant of insulin sensitivity in morbid-obese women. 61 54
19197257 2009
50
The effect of intragastric balloon on plasma ghrelin, leptin, and adiponectin levels in patients with morbid obesity. 54 61
19258408 2009
Sources

Variations for Leptin Deficiency or Dysfunction

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ClinVar genetic disease variations for Leptin Deficiency or Dysfunction:

6 (show top 50) (show all 78) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PPARG NM_001354669.1(PPARG):c.-180C>ASNV Pathogenic 8130 rs1800571 3:12422848-12422848 3:12381349-12381349
2 LEP LEP, 1-BP DEL, FS147TERdeletion Pathogenic 13986
3 LEP NM_000230.3(LEP):c.313C>T (p.Arg105Trp)SNV Pathogenic 13987 rs104894023 7:127894625-127894625 7:128254572-128254572
4 LEP NM_000230.3(LEP):c.298G>T (p.Asp100Tyr)SNV Pathogenic 162430 rs724159998 7:127894610-127894610 7:128254557-128254557
5 LEP NM_000230.3(LEP):c.461T>C (p.Leu154Pro)SNV Likely pathogenic 448905 rs1554394014 7:127894773-127894773 7:128254720-128254720
6 LEP NM_000230.3(LEP):c.165G>A (p.Gln55=)SNV Conflicting interpretations of pathogenicity 724209 7:127894477-127894477 7:128254424-128254424
7 LEP NM_000230.3(LEP):c.21C>T (p.Cys7=)SNV Conflicting interpretations of pathogenicity 358815 rs201523305 7:127892092-127892092 7:128252039-128252039
8 LEP NM_000230.3(LEP):c.*34G>ASNV Uncertain significance 358820 rs28954114 7:127894850-127894850 7:128254797-128254797
9 LEP NM_000230.3(LEP):c.*69A>GSNV Uncertain significance 358821 rs886061974 7:127894885-127894885 7:128254832-128254832
10 LEP NM_000230.3(LEP):c.*366A>TSNV Uncertain significance 358826 rs28954118 7:127895182-127895182 7:128255129-128255129
11 LEP NM_000230.3(LEP):c.*992G>TSNV Uncertain significance 358830 rs886061976 7:127895808-127895808 7:128255755-128255755
12 LEP NM_000230.3(LEP):c.*2527G>TSNV Uncertain significance 358848 rs886061979 7:127897343-127897343 7:128257290-128257290
13 LEP NM_000230.3(LEP):c.*2799C>TSNV Uncertain significance 358853 rs200887574 7:127897615-127897615 7:128257562-128257562
14 LEP NM_000230.3(LEP):c.212C>A (p.Thr71Asn)SNV Uncertain significance 358818 rs886061973 7:127894524-127894524 7:128254471-128254471
15 LEP NM_000230.3(LEP):c.*360G>ASNV Uncertain significance 358825 rs200748706 7:127895176-127895176 7:128255123-128255123
16 LEP NM_000230.3(LEP):c.*1640C>TSNV Uncertain significance 358837 rs201065449 7:127896456-127896456 7:128256403-128256403
17 LEP NM_000230.3(LEP):c.*1678C>TSNV Uncertain significance 358838 rs188857005 7:127896494-127896494 7:128256441-128256441
18 LEP NM_000230.3(LEP):c.*2224G>ASNV Uncertain significance 358843 rs28959472 7:127897040-127897040 7:128256987-128256987
19 LEP NM_000230.3(LEP):c.*2234G>ASNV Uncertain significance 358844 rs886061977 7:127897050-127897050 7:128256997-128256997
20 LEP NM_000230.3(LEP):c.*2267A>CSNV Uncertain significance 358846 rs886061978 7:127897083-127897083 7:128257030-128257030
21 LEP NM_000230.3(LEP):c.*2579G>ASNV Uncertain significance 358849 rs200738664 7:127897395-127897395 7:128257342-128257342
22 LEP NM_000230.3(LEP):c.*2595C>TSNV Uncertain significance 358851 rs28959475 7:127897411-127897411 7:128257358-128257358
23 LEP NM_000230.3(LEP):c.*2819_*2822dupduplication Uncertain significance 358856 rs56247456 7:127897620-127897621 7:128257567-128257568
24 LEP NM_000230.3(LEP):c.*1428C>ASNV Uncertain significance 358835 rs76601079 7:127896244-127896244 7:128256191-128256191
25 LEP NM_000230.3(LEP):c.*2822dupduplication Uncertain significance 358854 rs56247456 7:127897620-127897621 7:128257567-128257568
26 LEP NM_000230.3(LEP):c.-14T>GSNV Uncertain significance 909528 7:127892058-127892058 7:128252005-128252005
27 LEP NM_000230.3(LEP):c.53A>G (p.Tyr18Cys)SNV Uncertain significance 910456 7:127892124-127892124 7:128252071-128252071
28 LEP NM_000230.3(LEP):c.143C>T (p.Thr48Met)SNV Uncertain significance 910457 7:127892214-127892214 7:128252161-128252161
29 LEP NM_000230.3(LEP):c.436G>T (p.Ala146Ser)SNV Uncertain significance 911679 7:127894748-127894748 7:128254695-128254695
30 LEP NM_000230.3(LEP):c.*33C>TSNV Uncertain significance 911680 7:127894849-127894849 7:128254796-128254796
31 LEP NM_000230.3(LEP):c.*57C>TSNV Uncertain significance 911681 7:127894873-127894873 7:128254820-128254820
32 LEP NM_000230.3(LEP):c.*373G>ASNV Uncertain significance 909587 7:127895189-127895189 7:128255136-128255136
33 LEP NM_000230.3(LEP):c.*653A>CSNV Uncertain significance 910510 7:127895469-127895469 7:128255416-128255416
34 LEP NM_000230.3(LEP):c.*750G>CSNV Uncertain significance 910511 7:127895566-127895566 7:128255513-128255513
35 LEP NM_000230.3(LEP):c.*781G>CSNV Uncertain significance 910512 7:127895597-127895597 7:128255544-128255544
36 LEP NM_000230.3(LEP):c.*962T>GSNV Uncertain significance 911752 7:127895778-127895778 7:128255725-128255725
37 LEP NM_000230.3(LEP):c.*1124G>ASNV Uncertain significance 911753 7:127895940-127895940 7:128255887-128255887
38 LEP NM_000230.3(LEP):c.*1185C>TSNV Uncertain significance 911754 7:127896001-127896001 7:128255948-128255948
39 LEP NM_000230.3(LEP):c.*1318G>CSNV Uncertain significance 908787 7:127896134-127896134 7:128256081-128256081
40 LEP NM_000230.3(LEP):c.*1369G>TSNV Uncertain significance 908788 7:127896185-127896185 7:128256132-128256132
41 LEP NM_000230.3(LEP):c.*1422A>TSNV Uncertain significance 908789 7:127896238-127896238 7:128256185-128256185
42 LEP NM_000230.3(LEP):c.*1579G>ASNV Uncertain significance 909642 7:127896395-127896395 7:128256342-128256342
43 LEP NM_000230.3(LEP):c.*1637A>GSNV Uncertain significance 909643 7:127896453-127896453 7:128256400-128256400
44 LEP NM_000230.3(LEP):c.*1738G>ASNV Uncertain significance 910572 7:127896554-127896554 7:128256501-128256501
45 LEP NM_000230.3(LEP):c.*1749T>CSNV Uncertain significance 910573 7:127896565-127896565 7:128256512-128256512
46 LEP NM_000230.3(LEP):c.*1825T>CSNV Uncertain significance 910574 7:127896641-127896641 7:128256588-128256588
47 LEP NM_000230.3(LEP):c.*1886T>GSNV Uncertain significance 911808 7:127896702-127896702 7:128256649-128256649
48 LEP NM_000230.3(LEP):c.*2110G>TSNV Uncertain significance 908851 7:127896926-127896926 7:128256873-128256873
49 LEP NM_000230.3(LEP):c.*2245C>GSNV Uncertain significance 909706 7:127897061-127897061 7:128257008-128257008
50 LEP NM_000230.3(LEP):c.*2263G>ASNV Uncertain significance 909707 7:127897079-127897079 7:128257026-128257026

UniProtKB/Swiss-Prot genetic disease variations for Leptin Deficiency or Dysfunction:

73
# Symbol AA change Variation ID SNP ID
1 LEP p.Arg105Trp VAR_008094 rs104894023
2 LEP p.Asp100Tyr VAR_075144 rs724159998

Sources

Expression for Leptin Deficiency or Dysfunction

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Search GEO for disease gene expression data for Leptin Deficiency or Dysfunction.
Sources

Pathways for Leptin Deficiency or Dysfunction

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Pathways related to Leptin Deficiency or Dysfunction according to KEGG:

36
# Name Kegg Source Accession
1 Neuroactive ligand-receptor interaction hsa04080
2 Adipocytokine signaling pathway hsa04920
3 JAK-STAT signaling pathway hsa04630
4 AMPK signaling pathway hsa04152
5 Cytokine-cytokine receptor interaction hsa04060

Pathways related to Leptin Deficiency or Dysfunction according to GeneCards Suite gene sharing:

(show all 22)
# Super pathways Score Top Affiliating Genes
1
Signaling by GPCR 65
Show member pathways
 14 SH2B1 PYY POMC NPY MC4R MC3R
2
Peptide ligand-binding receptors 65
Show member pathways