LEPRD
MCID: LPT006
MIFTS: 48

Leptin Receptor Deficiency (LEPRD)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Leptin Receptor Deficiency

MalaCards integrated aliases for Leptin Receptor Deficiency:

Name: Leptin Receptor Deficiency 56 25 73 36 29 6 71
Obesity, Morbid, Due to Leptin Receptor Deficiency 56 25 13
Obesity Due to Leptin Receptor Gene Deficiency 25 58
Leprd 56 73
Morbid Obesity Due to Leptin Receptor Deficiency 73
Congenital Deficiency of the Leptin Receptor 25
Leptin Receptor-Related Monogenic Obesity 25
Obesity, Morbid, Nonsyndromic 2 25
Non-Syndromic Morbid Obesity 2 73
Deficiency, Leptin Receptor 39
Obesity, Morbid 56

Characteristics:

Orphanet epidemiological data:

58
obesity due to leptin receptor gene deficiency
Inheritance: Autosomal recessive;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset of severe hyperphagia and rapid weight gain from birth
bmi of males begins to decrease with onset of puberty
heterozygote lepr deficient individuals have increased fat mass


HPO:

31
leptin receptor deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare infertility disorders
Rare gynaecological and obstetric diseases
Rare endocrine diseases


Summaries for Leptin Receptor Deficiency

Genetics Home Reference : 25 Leptin receptor 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. The extreme hunger 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 leptin receptor deficiency also have hypogonadotropic hypogonadism, which is a condition caused by reduced production of hormones that direct sexual development. Affected individuals experience delayed puberty or do not go through puberty, and they may be unable to conceive children (infertile).

MalaCards based summary : Leptin Receptor Deficiency, also known as obesity, morbid, due to leptin receptor deficiency, is related to leptin deficiency or dysfunction and body mass index quantitative trait locus 11. An important gene associated with Leptin Receptor Deficiency is LEPR (Leptin Receptor), and among its related pathways/superpathways are Neuroactive ligand-receptor interaction and Adipocytokine signaling pathway. The drugs Octreotide and Nadroparin have been mentioned in the context of this disorder. Affiliated tissues include liver, pituitary and t cells, and related phenotypes are obesity and decreased serum leptin

OMIM : 56 Leptin receptor deficiency is characterized by severe early-onset obesity, major hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic dysfunction (summary by Dehghani et al., 2018). (614963)

KEGG : 36 Leptin receptor deficiency is an autosomal recessive condition that causes severe early-onset obesity and pituitary dysfunction. Mutations in LEPR gene encoding leptin receptor cause this disease.

UniProtKB/Swiss-Prot : 73 Leptin receptor deficiency: A rare disease characterized by normal levels of serum leptin, hyperphagia and severe obesity from an early age. Additional features include alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism.

Wikipedia : 74 Leptin receptor, also known as LEP-R or OB-R, is a type I cytokine receptor, a protein that in humans is... more...

Related Diseases for Leptin Receptor Deficiency

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

(showing 65, show less)
# Related Disease Score Top Affiliating Genes
1 leptin deficiency or dysfunction 29.0 LEPROT LEPR
2 body mass index quantitative trait locus 11 28.6 LEPROT LEPR
3 morbid obesity and spermatogenic failure 11.5
4 body mass index quantitative trait locus 9 10.5
5 body mass index quantitative trait locus 8 10.5
6 body mass index quantitative trait locus 4 10.5
7 body mass index quantitative trait locus 10 10.5
8 body mass index quantitative trait locus 7 10.5
9 body mass index quantitative trait locus 12 10.5
10 body mass index quantitative trait locus 14 10.5
11 body mass index quantitative trait locus 18 10.5
12 body mass index quantitative trait locus 19 10.5
13 body mass index quantitative trait locus 20 10.5
14 hyperglycemia 10.2
15 fatty liver disease, nonalcoholic 1 10.1
16 glucose intolerance 10.1
17 non-alcoholic fatty liver disease 10.0
18 hyperinsulinism 10.0
19 fatty liver disease 10.0
20 body mass index quantitative trait locus 1 10.0
21 bone resorption disease 10.0
22 breast cancer 9.8
23 osteoporosis 9.8
24 bone mineral density quantitative trait locus 8 9.8
25 microvascular complications of diabetes 3 9.8
26 microvascular complications of diabetes 4 9.8
27 microvascular complications of diabetes 6 9.8
28 microvascular complications of diabetes 7 9.8
29 bone mineral density quantitative trait locus 15 9.8
30 peripheral vascular disease 9.8
31 limb ischemia 9.8
32 sclerosteosis 9.8
33 hypogonadotropic hypogonadism 9.8
34 diabetic autonomic neuropathy 9.8
35 autonomic neuropathy 9.8
36 diabetic cataract 9.8
37 vascular disease 9.8
38 hypogonadism 9.8
39 lipid metabolism disorder 9.8
40 ischemia 9.8
41 myocarditis 9.8
42 vascular dementia 9.8
43 degenerative disc disease 9.8
44 cytokine deficiency 9.8
45 autonomic dysfunction 9.8
46 hypoxia 9.8
47 genetic obesity 9.8
48 sleep apnea 9.7
49 hereditary lymphedema i 9.7
50 bone disease 9.7
51 non-alcoholic steatohepatitis 9.7
52 heart disease 9.7
53 gestational diabetes 9.7
54 peptic esophagitis 9.7
55 avoidant personality disorder 9.7
56 personality disorder 9.7
57 liver disease 9.7
58 pustulosis of palm and sole 9.7
59 peripheral nervous system disease 9.7
60 peptic ulcer disease 9.7
61 eating disorder 9.7
62 neuropathy 9.7
63 psoriasis 9.7
64 achalasia 9.7
65 syndromic obesity 9.5 LEPROT LEPR

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



Diseases related to Leptin Receptor Deficiency

Symptoms & Phenotypes for Leptin Receptor Deficiency

Human phenotypes related to Leptin Receptor Deficiency:

58 31 (showing 30, show less)
# 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 aggressive behavior 31 obligate (100%) HP:0000718
4 abnormal hypothalamus morphology 31 obligate (100%) HP:0012286
5 primary amenorrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0000786
6 hyperinsulinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000842
7 gynecomastia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000771
8 decreased testicular size 58 31 hallmark (90%) Very frequent (99-80%) HP:0008734
9 hypergonadotropic hypogonadism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000815
10 decreased serum estradiol 58 31 hallmark (90%) Very frequent (99-80%) HP:0008214
11 polyphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002591
12 hypoplasia of the ovary 58 31 hallmark (90%) Very frequent (99-80%) HP:0008724
13 absence of secondary sex characteristics 58 31 hallmark (90%) Very frequent (99-80%) HP:0008187
14 decreased t cell activation 58 31 hallmark (90%) Very frequent (99-80%) HP:0005419
15 decreased serum testosterone level 31 hallmark (90%) HP:0040171
16 decreased proportion of cd4-positive helper t cells 31 hallmark (90%) HP:0005407
17 hypertriglyceridemia 58 31 frequent (33%) Frequent (79-30%) HP:0002155
18 recurrent upper respiratory tract infections 58 31 frequent (33%) Frequent (79-30%) HP:0002788
19 accelerated skeletal maturation 58 31 frequent (33%) Frequent (79-30%) HP:0005616
20 emotional lability 58 31 frequent (33%) Frequent (79-30%) HP:0000712
21 orthostatic hypotension due to autonomic dysfunction 58 31 frequent (33%) Frequent (79-30%) HP:0004926
22 pituitary hypothyroidism 58 31 frequent (33%) Frequent (79-30%) HP:0008245
23 insulin-resistant diabetes mellitus 58 31 frequent (33%) Frequent (79-30%) HP:0000831
24 diabetes mellitus 31 very rare (1%) HP:0000819
25 short stature 31 HP:0004322
26 delayed puberty 31 HP:0000823
27 growth hormone deficiency 31 HP:0000824
28 decreased testosterone in males 58 Very frequent (99-80%)
29 immune dysregulation 31 HP:0002958
30 decreased proportion of cd4-positive t cells 58 Very frequent (99-80%)

Symptoms via clinical synopsis from OMIM:

56
Endocrine Features:
hypogonadotropic hypogonadism
low estradiol
low testosterone
diabetes mellitus (in some patients)
low insulin-like growth factor 1 (in adults)
more
Abdomen Gastrointestinal:
hyperphagia

Respiratory:
upper respiratory tract infections

Growth Weight:
obesity, severe (onset from birth)

Genitourinary External Genitalia Male:
normal sexual and reproductive function

Immunology:
frequent childhood infections (predominantly upper respiratory tract)
reduction in absolute cd4+ t-cells
compensatory increase in cd19+ cell (b-cell) count
t-cells show reduced proliferative responses

Genitourinary Internal Genitalia Female:
irregular menses
delayed menses

Neurologic Behavioral Psychiatric Manifestations:
hyperphagia

Growth Height:
normal linear growth in childhood
short stature (final height)

Growth Other:
no pubertal growth spurt
bmi in males decreases around puberty

Genitourinary Internal Genitalia Male:
normal sexual and reproductive function

Clinical features from OMIM:

614963

MGI Mouse Phenotypes related to Leptin Receptor Deficiency:

45 (showing 1, show less)
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.62 LEPR LEPROT

Drugs & Therapeutics for Leptin Receptor Deficiency

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

(showing 319, show less)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Octreotide Approved, Investigational Phase 4 83150-76-9 383414 6400441
2
Nadroparin Approved, Investigational Phase 4
3
Dexmedetomidine Approved, Vet_approved Phase 4 113775-47-6 5311068 68602
4
Ibuprofen Approved Phase 4 15687-27-1 3672
5
chenodeoxycholic acid Approved Phase 4 474-25-9 10133
6
Ursodeoxycholic acid Approved, Investigational Phase 4 128-13-2 31401
7
Cefazolin Approved Phase 4 25953-19-9 656510 33255
8
Methylcobalamin Approved, Investigational Phase 4 13422-55-4
9
Hydroxocobalamin Approved Phase 4 13422-51-0 15589840 11953898
10
Morphine Approved, Investigational Phase 4 57-27-2 5288826
11
Clotrimazole Approved, Vet_approved Phase 4 23593-75-1 2812
12
Anidulafungin Approved, Investigational Phase 4 166663-25-8 166548
13
Miconazole Approved, Investigational, Vet_approved Phase 4 22916-47-8 4189
14
Atorvastatin Approved Phase 4 134523-00-5 60823
15
Micafungin Approved, Investigational Phase 4 235114-32-6 477468 3081921
16
Posaconazole Approved, Investigational, Vet_approved Phase 4 171228-49-2 147912
17
Liraglutide Approved Phase 4 204656-20-2 44147092
18
Chlorhexidine Approved, Vet_approved Phase 4 55-56-1 9552079 2713
19
Coal tar Approved Phase 4 8007-45-2
20
Amphotericin B Approved, Investigational Phase 4 1397-89-3 5280965 14956
21
Anastrozole Approved, Investigational Phase 4 120511-73-1 2187
22
Propofol Approved, Investigational, Vet_approved Phase 4 2078-54-8 4943
23
Rocuronium Approved Phase 4 119302-91-9, 143558-00-3 441290
24
Loperamide Approved Phase 4 53179-11-6 3955
25
Clarithromycin Approved Phase 4 81103-11-9 84029
26
Amoxicillin Approved, Vet_approved Phase 4 26787-78-0 33613
27
Bismuth subsalicylate Approved, Vet_approved Phase 4 14882-18-9 53629521
28
Remifentanil Approved Phase 4 132875-61-7 60815
29
Sevoflurane Approved, Vet_approved Phase 4 28523-86-6 5206
30
Fentanyl Approved, Illicit, Investigational, Vet_approved Phase 4 437-38-7 3345
31
Bupivacaine Approved, Investigational Phase 4 2180-92-9, 38396-39-3 2474
32
Ropivacaine Approved Phase 4 84057-95-4 71273 175805
33
Folic acid Approved, Nutraceutical, Vet_approved Phase 4 59-30-3 6037
34
Cyanocobalamin Approved, Nutraceutical Phase 4 68-19-9 44176380
35
Vitamin A Approved, Nutraceutical, Vet_approved Phase 4 22737-96-8, 68-26-8, 11103-57-4 9904001 445354
36
Cobalamin Experimental Phase 4 13408-78-1 6857388
37 Colesevelam Hydrochloride Phase 4
38 Hypolipidemic Agents Phase 4
39 Lipid Regulating Agents Phase 4
40 Anticholesteremic Agents Phase 4
41 Antimetabolites Phase 4
42 Adrenergic alpha-Agonists Phase 4
43 Adrenergic Agonists Phase 4
44 Hormones Phase 4
45 Analgesics Phase 4
46 Analgesics, Non-Narcotic Phase 4
47 Cyclooxygenase Inhibitors Phase 4
48 Antirheumatic Agents Phase 4
49 Anti-Inflammatory Agents Phase 4
50 Anti-Inflammatory Agents, Non-Steroidal Phase 4
51 Hypnotics and Sedatives Phase 4
52 Laxatives Phase 4
53 Cathartics Phase 4
54 Bile Acids and Salts Phase 4
55 Neuromuscular Blocking Agents Phase 4
56 Omega 3 Fatty Acid Phase 4
57 Hormone Antagonists Phase 4
58 Vitamin B Complex Phase 4
59 Vitamin B 12 Phase 4
60 Folate Phase 4
61 Vitamin B9 Phase 4
62 Vitamin B12 Phase 4
63 Antineoplastic Agents, Hormonal Phase 4
64 Antifungal Agents Phase 4
65 Antibiotics, Antitubercular Phase 4
66 Retinol palmitate Phase 4
67 Hematinics Phase 4
68 retinol Phase 4
69 Antiprotozoal Agents Phase 4
70 Antiparasitic Agents Phase 4
71 Garcinia Phase 4
72 Mangosteen Phase 4
73 Chlorhexidine gluconate Phase 4
74 Disinfectants Phase 4
75 Anti-Infective Agents, Local Phase 4
76 Liposomal amphotericin B Phase 4
77 Estrogen Antagonists Phase 4
78 Estrogen Receptor Antagonists Phase 4
79 Aromatase Inhibitors Phase 4
80 Estrogens Phase 4
81 Anesthetics Phase 4
82 Anesthetics, General Phase 4
83 Anesthetics, Intravenous Phase 4
84 Cytochrome P-450 Enzyme Inhibitors Phase 4
85 Anti-Infective Agents Phase 4
86 Anti-Bacterial Agents Phase 4
87 Antidiarrheals Phase 4
88 Cytochrome P-450 CYP3A Inhibitors Phase 4
89
Bismuth Phase 4 7440-69-9 16682734 105143
90 Anesthetics, Local Phase 4
91
Leucine Investigational, Nutraceutical Phase 4 61-90-5 6106
92
Nifedipine Approved Phase 2, Phase 3 21829-25-4 4485
93
Diltiazem Approved, Investigational Phase 2, Phase 3 42399-41-7 39186
94
Esmolol Approved Phase 2, Phase 3 103598-03-4, 81147-92-4 59768
95
Succinylcholine Approved Phase 2, Phase 3 306-40-1 5314
96
Levobupivacaine Approved, Investigational Phase 2, Phase 3 27262-47-1 92253
97
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
98 Coagulants Phase 3
99 Platelet Aggregation Inhibitors Phase 2, Phase 3
100 Narcotics Phase 2, Phase 3
101 Analgesics, Opioid Phase 2, Phase 3
102 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,... Phase 2, Phase 3
103 Sodium-Glucose Transporter 2 Inhibitors Phase 2, Phase 3
104
Arginine Investigational, Nutraceutical Phase 3 74-79-3 6322
105
Losartan Approved Phase 1, Phase 2 114798-26-4 3961
106
Dextromethorphan Approved Phase 1, Phase 2 125-71-3 5360696 5362449
107
Caffeine Approved Phase 1, Phase 2 58-08-2 2519
108
Amphetamine Approved, Illicit, Investigational Phase 2 300-62-9 5826 3007
109
Acetylcholine Approved, Investigational Phase 2 51-84-3 187
110
tannic acid Approved Phase 2 1401-55-4
111
Benzocaine Approved, Investigational Phase 2 94-09-7, 1994-09-7 2337
112
Exenatide Approved, Investigational Phase 2 141758-74-9 15991534
113
Phentermine Approved, Illicit Phase 2 122-09-8 4771
114
Topiramate Approved Phase 2 97240-79-4 5284627
115
Leuprolide Approved, Investigational Phase 2 53714-56-0 657181 3911
116 Cassava Phase 2
117 Sodium Channel Blockers Phase 2
118 Diuretics, Potassium Sparing Phase 2
119 Anti-Arrhythmia Agents Phase 2
120 Glucagon-Like Peptide 1 Phase 2
121 abobotulinumtoxinA Phase 2
122 Botulinum Toxins, Type A Phase 2
123 Botulinum Toxins Phase 2
124 Incretins Phase 2
125 Neurotransmitter Agents Phase 2
126 Anticonvulsants Phase 2
127 Central Nervous System Stimulants Phase 2
128 Adrenergic Agents Phase 2
129 Anti-Obesity Agents Phase 2
130 Hypoglycemic Agents Phase 2
131 Sympathomimetics Phase 2
132 Appetite Depressants Phase 2
133 Tin Fluorides Phase 2
134
Dopamine Approved Phase 1 51-61-6, 62-31-7 681
135
Acetaminophen Approved Phase 1 103-90-2 1983
136
Dalteparin Approved Phase 1 9005-49-6
137
Enoxaparin Approved Phase 1 9005-49-6 772
138
Rivaroxaban Approved Phase 1 366789-02-8
139
Calcifediol Approved, Nutraceutical Phase 1 19356-17-3 5283731 6433735
140 Fallypride Investigational Phase 1 166173-78-0
141
Talinolol Investigational Phase 1 57460-41-0 68770
142 Antihypertensive Agents Phase 1
143 Dopamine Agents Phase 1
144 Dopamine Antagonists Phase 1
145 Adrenergic Antagonists Phase 1
146 Adrenergic beta-Antagonists Phase 1
147 Antipyretics Phase 1
148 Pharmaceutical Solutions Phase 1
149 Heparin, Low-Molecular-Weight Phase 1
150 Hydroxycholecalciferols Phase 1
151
Desogestrel Approved 54024-22-5 40973
152
Heparin Approved, Investigational 9005-49-6 46507594 772
153
Atropine Approved, Vet_approved 51-55-8, 5908-99-6 174174
154
Magnesium Sulfate Approved, Investigational, Vet_approved 7487-88-9 24083
155
leucovorin Approved 58-05-9 6006 143
156
Nicotine Approved 54-11-5 942 89594
157
Repaglinide Approved, Investigational 135062-02-1 65981
158
Chlorzoxazone Approved 95-25-0 2733