MCID: OBS050
MIFTS: 18

Obesity Due to Congenital Leptin Deficiency

Categories: Metabolic diseases, Rare diseases

Aliases & Classifications for Obesity Due to Congenital Leptin Deficiency

MalaCards integrated aliases for Obesity Due to Congenital Leptin Deficiency:

Name: Obesity Due to Congenital Leptin Deficiency 54
Leptin Deficiency or Dysfunction 54 74
Obesity, Morbid, Nonsyndromic 1 54
Lepd 54

Classifications:



Summaries for Obesity Due to Congenital Leptin Deficiency

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 66628Disease definitionCongenital leptin deficiency is a form of monogenic obesity characterised by severe early-onset obesity and marked hyperphagia.EpidemiologyIt has been described in less than 30 patients.Clinical descriptionPatients 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.EtiologyLeptin 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 recessivetrait. 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 methodsFamily 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 treatmentCongenital 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.PrognosisAs 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 : Obesity Due to Congenital Leptin Deficiency, also known as leptin deficiency or dysfunction, is related to leptin deficiency or dysfunction and congenital leptin deficiency. The drugs Moxifloxacin and Zinc have been mentioned in the context of this disorder. Affiliated tissues include t cells, bone and ovary, and related phenotypes are obesity and decreased serum leptin

Related Diseases for Obesity Due to Congenital Leptin Deficiency

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

# Related Disease Score Top Affiliating Genes
1 leptin deficiency or dysfunction 11.6
2 congenital leptin deficiency 11.5

Symptoms & Phenotypes for Obesity Due to Congenital Leptin Deficiency

Human phenotypes related to Obesity Due to Congenital Leptin Deficiency:

33 (show all 20)
# Description HPO Frequency HPO Source Accession
1 obesity 33 obligate (100%) HP:0001513
2 decreased serum leptin 33 obligate (100%) HP:0003292
3 primary amenorrhea 33 hallmark (90%) HP:0000786
4 hyperinsulinemia 33 hallmark (90%) HP:0000842
5 hypergonadotropic hypogonadism 33 hallmark (90%) HP:0000815
6 absence of secondary sex characteristics 33 hallmark (90%) HP:0008187
7 decreased testicular size 33 hallmark (90%) HP:0008734
8 decreased serum testosterone level 33 hallmark (90%) HP:0040171
9 decreased proportion of cd4-positive t cells 33 hallmark (90%) HP:0005407
10 gynecomastia 33 hallmark (90%) HP:0000771
11 polyphagia 33 hallmark (90%) HP:0002591
12 decreased serum estradiol 33 hallmark (90%) HP:0008214
13 decreased t cell activation 33 hallmark (90%) HP:0005419
14 hypoplasia of the ovary 33 hallmark (90%) HP:0008724
15 hypertriglyceridemia 33 frequent (33%) HP:0002155
16 recurrent upper respiratory tract infections 33 frequent (33%) HP:0002788
17 accelerated skeletal maturation 33 frequent (33%) HP:0005616
18 insulin-resistant diabetes mellitus 33 frequent (33%) HP:0000831
19 orthostatic hypotension due to autonomic dysfunction 33 frequent (33%) HP:0004926
20 pituitary hypothyroidism 33 frequent (33%) HP:0008245

Drugs & Therapeutics for Obesity Due to Congenital Leptin Deficiency

Drugs for Obesity Due to Congenital Leptin Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Moxifloxacin Approved, Investigational Phase 2 354812-41-2, 151096-09-2 152946
2
Zinc Approved, Investigational Phase 2 7440-66-6 32051
3 Contraceptive Agents Phase 2
4 Contraceptives, Oral Phase 2
5 Norgestimate, ethinyl estradiol drug combination Phase 2
6 Contraceptives, Oral, Combined Phase 2
7 Insulin, Globin Zinc Phase 2,Not Applicable
8 insulin Phase 2,Not Applicable
9 Hypoglycemic Agents Phase 2

Interventional clinical trials:

(show all 13)
# Name Status NCT ID Phase Drugs
1 Low-Dose Leptin and the Formerly-Obese Unknown status NCT00073242 Phase 3 Leptin;T3 repletion
2 Compassionate Use of Metreleptin in Previously Treated People With Partial Lipodystrophy Enrolling by invitation NCT02262806 Phase 3 Metreleptin
3 Effects of Human Leptin Replacement Unknown status NCT00657605 Phase 2 Recombinant methionyl human leptin
4 Effects of Leptin Replacement in Children Unknown status NCT00659828 Phase 2 Recombinant methionyl human leptin
5 Study of Leptin for the Treatment of Hypothalamic Amenorrhea Completed NCT00130117 Phase 2 r-metHuLeptin;Oral Contraceptive Pills (OCPs)
6 Trial of Leptin Administration After Roux-en-Y Gastric Bypass Completed NCT00710814 Phase 1, Phase 2 Leptin
7 Leptin to Treat Lipodystrophy Completed NCT00025883 Phase 2 Metreleptin
8 Leptin to Treat Lipodystrophy Completed NCT00005905 Phase 2 hu Leptin (A-100)
9 Effect of Leptin Therapy in the Treatment of Severe Insulin Resistance Recruiting NCT00085982 Phase 2 Metreleptin
10 Expanded Access Metreleptin Study Active, not recruiting NCT02404896 Phase 2 Metreleptin
11 Leptin in Human Energy and Neuroendocrine Homeostasis Unknown status NCT00265980 Not Applicable Placebo;Leptin;placebo;Tri-iodothyronine
12 Recombinant Human Leptin Therapy Effects on Insulin Action Completed NCT01207934 Not Applicable low-dose leptin;high-dose leptin
13 Setemelanotide in a Single Patient With Partial Lipodystrophy No longer available NCT03262610 Setmelanotide

Search NIH Clinical Center for Obesity Due to Congenital Leptin Deficiency

Genetic Tests for Obesity Due to Congenital Leptin Deficiency

Anatomical Context for Obesity Due to Congenital Leptin Deficiency

MalaCards organs/tissues related to Obesity Due to Congenital Leptin Deficiency:

42
T Cells, Bone, Ovary, Pituitary

Publications for Obesity Due to Congenital Leptin Deficiency

Variations for Obesity Due to Congenital Leptin Deficiency

Expression for Obesity Due to Congenital Leptin Deficiency

Search GEO for disease gene expression data for Obesity Due to Congenital Leptin Deficiency.

Pathways for Obesity Due to Congenital Leptin Deficiency

GO Terms for Obesity Due to Congenital Leptin Deficiency

Sources for Obesity Due to Congenital Leptin Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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