HH23
MCID: HYP763
MIFTS: 41

Hypogonadotropic Hypogonadism 23 Without Anosmia (HH23)

Categories: Cardiovascular diseases, Ear diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Hypogonadotropic Hypogonadism 23 Without Anosmia

MalaCards integrated aliases for Hypogonadotropic Hypogonadism 23 Without Anosmia:

Name: Hypogonadotropic Hypogonadism 23 Without Anosmia 57 72
Fertile Eunuch Syndrome 57 12 20 72 36 13 6
Hypogonadotropic Hypogonadism 23 with or Without Anosmia 57 12 29 15
Pasqualini Syndrome 57 12 72
46,xy Disorder of Sex Development Due to Luteinizing Hormone Subunit Beta Deficiency 12 58
Leydig Cell Hypoplasia Due to Luteinizing Hormone Subunit Beta Deficiency 12 58
46,xy Dsd Due to Luteinizing Hormone Subunit Beta Deficiency 12 58
46,xy Disorder of Sex Development Due to Lhb Deficiency 12 58
Leydig Cell Hypoplasia Due to Lhb Deficiency 12 58
46,xy Dsd Due to Lhb Deficiency 12 58
Hh23 57 72
Eunuchoidism with Spermatogenesis, Normal Fsh and Low or Normal Interstitial Cell-Stimulating Hormone 20
Isolated Lutropin Deficiency 70

Characteristics:

OMIM®:

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

Miscellaneous:
some male patients exhibit some degree of spermatogenesis, hence the designation 'fertile eunuch syndrome' has been used
affected females have apparently normal puberty but later develop secondary amenorrhea with anovulatory cycles


HPO:

31
hypogonadotropic hypogonadism 23 without anosmia:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare infertility disorders
Rare endocrine diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0090091
OMIM® 57 228300
OMIM Phenotypic Series 57 PS147950
KEGG 36 H01973
MeSH 44 D005058
ICD10 32 Q56.1
ICD10 via Orphanet 33 Q56.1
Orphanet 58 ORPHA325448
MedGen 41 C0271582
UMLS 70 C0271582

Summaries for Hypogonadotropic Hypogonadism 23 Without Anosmia

OMIM® : 57 Male patients with hypogonadotropic hypogonadism due to isolated luteinizing hormone (LH) deficiency have normal sexual differentiation but fail to develop spontaneous puberty. Absence of LH alters Leydig cell proliferation and maturation and impairs the onset of normal spermatogenesis, which requires high levels of intratesticular testosterone. Infertility and very low levels of spermatogenesis generally persist in affected men despite long-term exposure to gonadotropin therapy. Female patients exhibit normal pubertal development and menarche, followed by oligomenorrhea and anovulatory secondary amenorrhea (summary by Basciani et al., 2012). For a general phenotypic description and discussion of genetic heterogeneity of hypogonadotropic hypogonadism, see 147950. (228300) (Updated 20-May-2021)

MalaCards based summary : Hypogonadotropic Hypogonadism 23 Without Anosmia, also known as fertile eunuch syndrome, is related to hypogonadism and clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly. An important gene associated with Hypogonadotropic Hypogonadism 23 Without Anosmia is LHB (Luteinizing Hormone Subunit Beta), and among its related pathways/superpathways are Ovarian steroidogenesis and Prolactin signaling pathway. Affiliated tissues include testes, pituitary and uterus, and related phenotypes are secondary amenorrhea and micropenis

Disease Ontology : 12 A hypogonadotropic hypogonadism that has material basis in homozygous or compound heterozygous mutation in the LHB gene on chromosome 19q13.

KEGG : 36 Fertile eunuch syndrome is a form of idiopathic hypogonadotropic hypogonadism in males. It is characterized by eunuchoid features associated with normal or low-normal sized testes, presence of active spermatogenesis despite the absence or scarcity of Leydig cells, and androgenic response (clinical or chemical or both) to administered human chorionic gonadotropin. In this disease, the levels of testosterone and follicle-stimulating hormone (FSH) are inadequate to induce spermatogenesis and the development of secondary sexual characteristics. Mutations in the beta subunit of luteinizing hormone gene have been identified from patients of this disease.

UniProtKB/Swiss-Prot : 72 Hypogonadotropic hypogonadism 23 without anosmia: A form of hypogonadotropic hypogonadism, a group of disorders characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. HH23 male patients have normal sexual differentiation, reduced or absent Leydig cells, reduced or absent spermatogenesis, and absence of spontaneous puberty. Female patients exhibit normal pubertal development and menarche, followed by oligomenorrhea and anovulatory secondary amenorrhea.

Related Diseases for Hypogonadotropic Hypogonadism 23 Without Anosmia

Diseases in the Hypogonadotropic Hypogonadism 7 with or Without Anosmia family:

Hypogonadotropic Hypogonadism 2 with or Without Anosmia Hypogonadotropic Hypogonadism 23 Without Anosmia
Hypogonadotropic Hypogonadism 24 Without Anosmia Hypogonadotropic Hypogonadism 3 with or Without Anosmia
Hypogonadotropic Hypogonadism 1 with or Without Anosmia Hypogonadotropic Hypogonadism 4 with or Without Anosmia
Hypogonadotropic Hypogonadism 5 with or Without Anosmia Hypogonadotropic Hypogonadism 6 with or Without Anosmia
Hypogonadotropic Hypogonadism 8 with or Without Anosmia Hypogonadotropic Hypogonadism 9 with or Without Anosmia
Hypogonadotropic Hypogonadism 10 with or Without Anosmia Hypogonadotropic Hypogonadism 11 with or Without Anosmia
Hypogonadotropic Hypogonadism 12 with or Without Anosmia Hypogonadotropic Hypogonadism 13 with or Without Anosmia
Hypogonadotropic Hypogonadism 14 with or Without Anosmia Hypogonadotropic Hypogonadism 15 with or Without Anosmia
Hypogonadotropic Hypogonadism 16 with or Without Anosmia Hypogonadotropic Hypogonadism 17 with or Without Anosmia
Hypogonadotropic Hypogonadism 18 with or Without Anosmia Hypogonadotropic Hypogonadism 19 with or Without Anosmia
Hypogonadotropic Hypogonadism 20 with or Without Anosmia Hypogonadotropic Hypogonadism 21 with or Without Anosmia
Hypogonadotropic Hypogonadism 22 with or Without Anosmia

Diseases related to Hypogonadotropic Hypogonadism 23 Without Anosmia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 42)
# Related Disease Score Top Affiliating Genes
1 hypogonadism 29.1 PROKR2 LHB GNRHR GNRH1 ANOS1
2 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 10.1
3 clubfoot 10.1
4 eunuchism 10.1
5 congenital hypogonadotropic hypogonadism 10.0 GNRHR ANOS1
6 pseudohermaphroditism 9.9 LHB EPPIN
7 choanal atresia, posterior 9.9 PROKR2 ANOS1
8 atrophy of prostate 9.9 GNRH1 EPPIN
9 estrogen excess 9.9 GNRH1 EPPIN
10 isolated gonadotropin-releasing hormone deficiency 9.8 GNRHR GNRH1
11 pelvic varices 9.8 GNRH1 EPPIN
12 sexual disorder 9.8 GNRH1 EPPIN
13 hypothalamic hamartomas 9.8 GNRHR GNRH1
14 uterine benign neoplasm 9.8 GNRH1 EPPIN
15 reproductive organ benign neoplasm 9.8 GNRH1 EPPIN
16 precocious puberty, male-limited 9.8 GNRHR GNRH1
17 aromatase excess syndrome 9.8 GNRH1 EPPIN
18 testicular disease 9.8 GNRH1 EPPIN
19 impotence 9.8 GNRH1 EPPIN
20 coloboma of optic nerve 9.7 PROKR2 GNRH1
21 coloboma of macula 9.6 PROKR2 GNRHR ANOS1
22 ectopic pregnancy 9.6 PROKR2 GNRH1
23 amenorrhea 9.6 LHB GNRHR GNRH1
24 adrenal hypoplasia, congenital 9.6 GNRHR GNRH1 EPPIN
25 oligospermia 9.6 GNRHR GNRH1 EPPIN
26 46,xy sex reversal 9.6 GNRHR GNRH1
27 hypopituitarism 9.6 PROKR2 GNRH1
28 vas deferens, congenital bilateral aplasia of 9.6 PROKR2 ANOS1
29 male infertility 9.6 LHB GNRH1 EPPIN
30 premature menopause 9.5 GNRHR GNRH1 EPPIN
31 orofacial cleft 9.5 PROKR2 GNRH1 ANOS1
32 infertility 9.4 LHB GNRHR GNRH1 EPPIN
33 hypogonadotropic hypogonadism 7 with or without anosmia 9.2 PROKR2 GNRHR GNRH1 ANOS1
34 normosmic congenital hypogonadotropic hypogonadism 9.2 PROKR2 GNRHR GNRH1 ANOS1
35 septooptic dysplasia 9.2 PROKR2 GNRHR GNRH1 ANOS1
36 charge syndrome 9.2 PROKR2 GNRHR GNRH1 ANOS1
37 renal hypodysplasia/aplasia 1 9.2 PROKR2 GNRHR GNRH1 ANOS1
38 kallmann syndrome 9.2 PROKR2 GNRHR GNRH1 ANOS1
39 sensorineural hearing loss 9.2 PROKR2 GNRHR GNRH1 ANOS1
40 hypogonadotropic hypogonadism 9.0 PROKR2 LHB GNRHR GNRH1 ANOS1
41 disorder of sexual development 9.0 PROKR2 GNRHR GNRH1 EPPIN ANOS1
42 cryptorchidism, unilateral or bilateral 9.0 PROKR2 GNRHR GNRH1 EPPIN ANOS1

Graphical network of the top 20 diseases related to Hypogonadotropic Hypogonadism 23 Without Anosmia:



Diseases related to Hypogonadotropic Hypogonadism 23 Without Anosmia

Symptoms & Phenotypes for Hypogonadotropic Hypogonadism 23 Without Anosmia

Human phenotypes related to Hypogonadotropic Hypogonadism 23 Without Anosmia:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 secondary amenorrhea 31 HP:0000869
2 micropenis 31 HP:0000054
3 gynecomastia 31 HP:0000771
4 abnormality of metabolism/homeostasis 31 HP:0001939
5 sparse axillary hair 31 HP:0002215
6 sparse pubic hair 31 HP:0002225
7 decreased serum testosterone level 31 HP:0040171
8 abnormal spermatogenesis 31 HP:0008669
9 abnormality of the leydig cells 31 HP:0010789
10 ovarian cyst 31 HP:0000138
11 androgen insufficiency 31 HP:0008226
12 oligomenorrhea 31 HP:0000876
13 decreased circulating luteinizing hormone level 31 HP:0030344
14 hypogonadotropic hypogonadism 31 HP:0000044
15 testicular microlithiasis 31 HP:0012215

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Genitourinary Internal Genitalia Female:
secondary amenorrhea
oligomenorrhea after menarche
small to normal uterus
multicystic ovaries

Endocrine Features:
hypogonadotropic hypogonadism
low testosterone levels
delayed or absent puberty in males
spontaneous normal puberty in females
low to undetectable luteinizing hormone levels
more
Genitourinary External Genitalia Male:
small penis

Skin Nails Hair Hair:
sparse to absent male facial hair
sparse to absent axillary hair
sparse to absent pubic hair

Chest Breasts:
gynecomastia

Genitourinary Internal Genitalia Male:
testicular microlithiasis
small or normal testes
low semen volume
reduced or absent spermatogenesis
reduced or absent leydig cells

Head And Neck Nose:
normal sense of smell

Voice:
juvenile voice

Clinical features from OMIM®:

228300 (Updated 20-May-2021)

Drugs & Therapeutics for Hypogonadotropic Hypogonadism 23 Without Anosmia

Search Clinical Trials , NIH Clinical Center for Hypogonadotropic Hypogonadism 23 Without Anosmia

Genetic Tests for Hypogonadotropic Hypogonadism 23 Without Anosmia

Genetic tests related to Hypogonadotropic Hypogonadism 23 Without Anosmia:

# Genetic test Affiliating Genes
1 Hypogonadotropic Hypogonadism 23 with or Without Anosmia 29

Anatomical Context for Hypogonadotropic Hypogonadism 23 Without Anosmia

MalaCards organs/tissues related to Hypogonadotropic Hypogonadism 23 Without Anosmia:

40
Testes, Pituitary, Uterus, Prostate

Publications for Hypogonadotropic Hypogonadism 23 Without Anosmia

Articles related to Hypogonadotropic Hypogonadism 23 Without Anosmia:

(show all 25)
# Title Authors PMID Year
1
Hypogonadism in a patient with two novel mutations of the luteinizing hormone β-subunit gene expressed in a compound heterozygous form. 6 57
22723313 2012
2
Normal spermatogenesis in a man with mutant luteinizing hormone. 57 6
19890128 2009
3
Testicular effects of isolated luteinizing hormone deficiency and reversal by long-term human chorionic gonadotropin treatment. 57 6
19126631 2009
4
Luteinizing hormone beta mutation and hypogonadism in men and women. 57 6
17761593 2007
5
Hypogonadism in a patient with a mutation in the luteinizing hormone beta-subunit gene. 6 57
15602022 2004
6
Hypogonadism caused by a single amino acid substitution in the beta subunit of luteinizing hormone. 6 57
1727547 1992
7
Hypogonadism in a male with immunologically active, biologically inactive luteinizing hormone: an exception to a venerable rule. 57 6
429481 1979
8
The "fertile eunuch" syndrome: demonstration of isolated luteinizing hormone deficiency by radioimmunoassay technique. 57 61
5710591 1968
9
Inactivating mutations of luteinizing hormone beta-subunit or luteinizing hormone receptor cause oligo-amenorrhea and infertility in women. 57
19129711 2009
10
Hypogonadism in a male with an immunologically active, biologically inactive luteinizing hormone: characterization of the abnormal hormone. 57
6785294 1981
11
A case of male pseudohermaphroditism associated with elevated LH, normal FSH and low testosterone possibly due to the secretion of an abnormal LH molecule. 57
989221 1976
12
A syndrome of eunuchoidism with spermatogenesis, normal urinary FSH and low or normal ICSH: (fertile eunuchs). 57
13061573 1953
13
Hypoandrogenic syndrome with normal spermatogenesis. 57
13022759 1953
14
[Pasqualini's syndrome: hypoandrogenism with spermatogenesis]. 61
25637904 2015
15
Was Akhenaten really sick? 61
23810106 2013
16
Fertile eunuch syndrome in association with biventricular noncompaction, bicuspid aortic valve, severe aortic stenosis, and talipes equinovarus. 61
23678225 2013
17
Fertile eunuch syndrome with the mutations (Trp8Arg and Ile15Thr) in the beta subunit of luteinizing hormone. 61
14709845 2003
18
The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor. 61
11397842 2001
19
Induction of spermatogenesis with gonadotrophins in Chinese men with hypogonadotrophic hypogonadism. 61
7698849 1994
20
[Fertile eunuch syndrome]. 61
7757789 1993
21
[Hypogonadism with spermatogenesis (fertile eunuch syndrome) (author's transl)]. 61
6283650 1982
22
HLA-compatible paternity in two "fertile eunuchs" with congenital hypogonadotropic hypogonadism and anosmia (the Kallmann syndrome). 61
6772660 1980
23
Fertile eunuch syndrome versus classic hypogonadotrophic hypogonadism. 61
343467 1978
24
The fertile eunuch syndrome. An isolated leydig-cell failure? 61
883676 1977
25
Effect of synthetic gonadotropin-releasing hormone (GnRH) in a patient with the "fertile eunuch" syndrome. 61
1097462 1975

Variations for Hypogonadotropic Hypogonadism 23 Without Anosmia

ClinVar genetic disease variations for Hypogonadotropic Hypogonadism 23 Without Anosmia:

6 (show all 11)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LHB NM_000894.2(LHB):c.221A>G (p.Gln74Arg) SNV Pathogenic 14413 rs5030773 GRCh37: 19:49519530-49519530
GRCh38: 19:49016273-49016273
2 LHB NM_000894.2(LHB):c.167G>A (p.Gly56Asp) SNV Pathogenic 14416 rs121912517 GRCh37: 19:49519820-49519820
GRCh38: 19:49016563-49016563
3 LHB NM_000894.2(LHB):c.183+1G>T SNV Pathogenic 189293 rs786204822 GRCh37: 19:49519803-49519803
GRCh38: 19:49016546-49016546
4 LHB NM_000894.2(LHB):c.28_39del (p.Leu10_Leu13del) Deletion Pathogenic 189292 rs769066903 GRCh37: 19:49519948-49519959
GRCh38: 19:49016691-49016702
5 LHB NM_000894.2(LHB):c.88_96del (p.His30_Ile32del) Deletion Pathogenic 189291 rs786204823 GRCh37: 19:49519891-49519899
GRCh38: 19:49016634-49016642
6 LHB NM_000894.2(LHB):c.183+1G>C SNV Pathogenic 189290 rs786204822 GRCh37: 19:49519803-49519803
GRCh38: 19:49016546-49016546
7 LHB NM_000894.3(LHB):c.286G>A (p.Val96Met) SNV Uncertain significance 818213 rs149003040 GRCh37: 19:49519465-49519465
GRCh38: 19:49016208-49016208
8 LHB NM_000894.2(LHB):c.16-26T>C SNV Benign 518304 rs4002462 GRCh37: 19:49519997-49519997
GRCh38: 19:49016740-49016740
9 LHB NM_000894.2(LHB):c.183+11T>C SNV Benign 518301 rs2387588 GRCh37: 19:49519793-49519793
GRCh38: 19:49016536-49016536
10 LHB NM_000894.2(LHB):c.132A>C (p.Pro44=) SNV Benign 518302 rs1056914 GRCh37: 19:49519855-49519855
GRCh38: 19:49016598-49016598
11 LHB NM_000894.2(LHB):c.114C>G (p.Val38=) SNV Benign 518303 rs6521 GRCh37: 19:49519873-49519873
GRCh38: 19:49016616-49016616

UniProtKB/Swiss-Prot genetic disease variations for Hypogonadotropic Hypogonadism 23 Without Anosmia:

72
# Symbol AA change Variation ID SNP ID
1 LHB p.Gln74Arg VAR_003189 rs5030773

Expression for Hypogonadotropic Hypogonadism 23 Without Anosmia

Search GEO for disease gene expression data for Hypogonadotropic Hypogonadism 23 Without Anosmia.

Pathways for Hypogonadotropic Hypogonadism 23 Without Anosmia

Pathways related to Hypogonadotropic Hypogonadism 23 Without Anosmia according to KEGG:

36
# Name Kegg Source Accession
1 Ovarian steroidogenesis hsa04913
2 Prolactin signaling pathway hsa04917

GO Terms for Hypogonadotropic Hypogonadism 23 Without Anosmia

Cellular components related to Hypogonadotropic Hypogonadism 23 Without Anosmia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 8.92 LHB GNRH1 EPPIN ANOS1

Biological processes related to Hypogonadotropic Hypogonadism 23 Without Anosmia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of peptidase activity GO:0010466 8.96 EPPIN ANOS1
2 G protein-coupled receptor signaling pathway GO:0007186 8.92 PROKR2 LHB GNRHR GNRH1

Molecular functions related to Hypogonadotropic Hypogonadism 23 Without Anosmia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptidase inhibitor activity GO:0030414 9.16 EPPIN ANOS1
2 hormone activity GO:0005179 8.96 LHB GNRH1
3 serine-type endopeptidase inhibitor activity GO:0004867 8.62 EPPIN ANOS1

Sources for Hypogonadotropic Hypogonadism 23 Without Anosmia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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