MCID: HYP438
MIFTS: 29

Hyperaldosteronism, Familial, Type Iii

Categories: Genetic diseases, Rare diseases, Endocrine diseases, Cardiovascular diseases, Nephrological diseases

Aliases & Classifications for Hyperaldosteronism, Familial, Type Iii

MalaCards integrated aliases for Hyperaldosteronism, Familial, Type Iii:

Name: Hyperaldosteronism, Familial, Type Iii 57 13 40 73
Familial Hyperaldosteronism Type 3 53 59 29 6 73
Familial Hyperaldosteronism Type Iii 53 59 75
Fh Iii 57 53 75
Fh3 53 59 75
Fh-Iii 53 59
Hald3 57 75
Hyperaldosteronism, Familial, 3 75
Familial Hyperaldosteronism 3 75
Fh Type Iii 75

Characteristics:

Orphanet epidemiological data:

59
familial hyperaldosteronism type iii
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Childhood,Infancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset of symptoms in first decade of life
patients with medication-resistant hypertension require bilateral adrenalectomy


HPO:

32
hyperaldosteronism, familial, type iii:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 59  
Rare endocrine diseases


Summaries for Hyperaldosteronism, Familial, Type Iii

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 251274Disease definitionFamilial hyperaldosteronism type III (FH-III) is a rare heritable form of primary aldosteronism (PA) that is characterized by early-onset severe hypertension, non glucocorticoid-remediable hyperaldosteronism, overproduction of 18-oxocortisol and 18-hydroxycortisol, and profound hypokalemia.EpidemiologySeven families with FH-III have been reported to date.Clinical descriptionSevere hypertension associated with profound hypokalemia generally manifests during early childhood. It can be accompanied with polydipsia, polyuria, nausea, vomiting and headaches. Marked bilateral adrenal hyperplasia has been described. In exceptional cases, a mild form of FH-III, resembling to FH type II (see this term) has been reported, with normal appearing adrenals and treatable with medical therapy.EtiologyFH-III is due to heterozygousmissense mutations of the KCNJ5 gene (11q24), encoding the G-protein-activated inward rectifier potassium channel GIRK-4. These mutations result in loss of channel selectivity, membrane depolarization of the zona glomerulosa cells of the adrenal cortex, opening of voltage-activated calcium channels, and activation of the calcium signaling pathway that trigger saldosterone biosynthesis. There is a genotype-phenotype correlation, with the mild phenotype observed in patients with the p.G151E and p.Y152C mutations.Diagnostic methodsBlood and urinary tests show profound hypokalemia, an abnormal aldosterone/renin ratio with increased aldosterone levels not suppressible by dexamethasone, suppressed plasma renin activity, and elevated levels of the hybrid steroids 18-oxo- and 18-hydroxycortisol. Diagnosis is confirmed by genetic testing.Differential diagnosisThe clinical presentation resembles that of the other familial forms of hyperaldosteronism (FH-I, FH-II) (see these terms).Genetic counselingTransmission is autosomal dominant.Management and treatmentFH-III does not respond to glucocorticoid treatment. Severe cases require bilateral adrenalectomy to normalize blood pressure and hypokalemia, whereas mild cases are treated with medical therapy with aldosterone antagonists and/or other antihypertensive drugs if required.PrognosisIn severe cases treated with bilateral adrenalectomy, life-long glucocorticoid and mineralocorticoid replacement therapy is required. In mild cases, prognosis is good with medical treatment.Visit the Orphanet disease page for more resources.

MalaCards based summary : Hyperaldosteronism, Familial, Type Iii, also known as familial hyperaldosteronism type 3, is related to hyperaldosteronism, familial, type ii and hypercholesterolemia, autosomal dominant, 3. An important gene associated with Hyperaldosteronism, Familial, Type Iii is KCNJ5 (Potassium Voltage-Gated Channel Subfamily J Member 5). Affiliated tissues include testes, cortex and adrenal cortex, and related phenotypes are hypertension and muscle weakness

OMIM : 57 This form of hyperaldosteronism is characterized by hypertension secondary to massive adrenal mineralocorticoid production. Like patients with glucocorticoid-remediable aldosteronism (GRA, or FH I; 103900), patients with FH III present with childhood hypertension, elevated aldosteronism levels, and high levels of the hybrid steroids 18-oxocortisol and 18-hydroxycortisol. However, hypertension and aldosteronism in FH III are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy to control hypertension (Geller et al., 2008). (613677)

UniProtKB/Swiss-Prot : 75 Hyperaldosteronism, familial, 3: A form of hyperaldosteronism characterized by hypertension secondary to massive adrenal mineralocorticoid production. HALD3 patients present with childhood hypertension, elevated aldosteronism levels, and high levels of the hybrid steroids 18-oxocortisol and 18- hydroxycortisol. Hypertension and aldosteronism are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy to control hypertension.

Related Diseases for Hyperaldosteronism, Familial, Type Iii

Diseases in the Familial Hyperaldosteronism family:

Hyperaldosteronism, Familial, Type I Hyperaldosteronism, Familial, Type Ii
Hyperaldosteronism, Familial, Type Iii Hyperaldosteronism, Familial, Type Iv

Diseases related to Hyperaldosteronism, Familial, Type Iii via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hyperaldosteronism, familial, type ii 11.2
2 hypercholesterolemia, autosomal dominant, 3 10.9
3 familial hyperaldosteronism 10.2
4 conn's syndrome 9.9

Symptoms & Phenotypes for Hyperaldosteronism, Familial, Type Iii

Symptoms via clinical synopsis from OMIM:

57
Laboratory Abnormalities:
hypokalemia
decreased plasma renin activity
hypercalciuria (in some patients)
paradoxical increase or no change in serum aldosterone and blood pressure after dexamethasone administration

Cardiovascular Vascular:
hypertension, severe

Endocrine Features:
adrenal hyperplasia, bilateral
elevated serum aldosterone
elevated 18-hydroxycortisol
elevated 18-oxocortisol

Metabolic Features:
metabolic acidosis (in some patients)
polydipsia (in some patients)

Genitourinary Kidneys:
adrenal hyperplasia, bilateral
elevated aldosterone secretion
hyperplasia of zona fasciculata of adrenal gland
hyperplasia of zona glomerulosa of adrenal gland
atrophic zona glomerulosa of adrenal gland (rare)
more
Muscle Soft Tissue:
muscle weakness, hypokalemia-related


Clinical features from OMIM:

613677

Human phenotypes related to Hyperaldosteronism, Familial, Type Iii:

59 32 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertension 59 32 obligate (100%) Obligate (100%) HP:0000822
2 muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0001324
3 polydipsia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001959
4 hypokalemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002900
5 prolonged qt interval 59 32 occasional (7.5%) Occasional (29-5%) HP:0001657
6 hypercalciuria 59 32 occasional (7.5%) Occasional (29-5%) HP:0002150
7 left ventricular hypertrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001712
8 epistaxis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000421
9 intracranial hemorrhage 59 32 occasional (7.5%) Occasional (29-5%) HP:0002170
10 headache 59 32 occasional (7.5%) Occasional (29-5%) HP:0002315
11 tinnitus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000360
12 adrenal hyperplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0008221
13 abnormal circulating renin 59 32 obligate (100%) Obligate (100%) HP:0040084
14 nausea 59 32 occasional (7.5%) Occasional (29-5%) HP:0002018
15 glucocortocoid-insensitive primary hyperaldosteronism 59 32 hallmark (90%) Very frequent (99-80%) HP:0011740
16 metabolic alkalosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0200114
17 hyperaldosteronism 32 HP:0000859
18 metabolic acidosis 32 occasional (7.5%) HP:0001942
19 dexamethasone-suppresible primary hyperaldosteronism 59 Excluded (0%)
20 decreased circulating renin level 32 HP:0003351
21 polyuria 32 occasional (7.5%) HP:0000103

Drugs & Therapeutics for Hyperaldosteronism, Familial, Type Iii

Search Clinical Trials , NIH Clinical Center for Hyperaldosteronism, Familial, Type Iii

Genetic Tests for Hyperaldosteronism, Familial, Type Iii

Genetic tests related to Hyperaldosteronism, Familial, Type Iii:

# Genetic test Affiliating Genes
1 Familial Hyperaldosteronism Type 3 29 KCNJ5

Anatomical Context for Hyperaldosteronism, Familial, Type Iii

MalaCards organs/tissues related to Hyperaldosteronism, Familial, Type Iii:

41
Testes, Cortex, Adrenal Cortex, Adrenal Gland

Publications for Hyperaldosteronism, Familial, Type Iii

Articles related to Hyperaldosteronism, Familial, Type Iii:

# Title Authors Year
1
Disordered zonal and cellular CYP11B2 enzyme expression in familial hyperaldosteronism type 3. ( 27793677 )
2017

Variations for Hyperaldosteronism, Familial, Type Iii

UniProtKB/Swiss-Prot genetic disease variations for Hyperaldosteronism, Familial, Type Iii:

75
# Symbol AA change Variation ID SNP ID
1 KCNJ5 p.Gly151Arg VAR_065930 rs386352319
2 KCNJ5 p.Thr158Ala VAR_065931 rs387906778
3 KCNJ5 p.Gly151Glu VAR_067090 rs587777437
4 KCNJ5 p.Tyr152Cys VAR_077577
5 KCNJ5 p.Ile157Ser VAR_077578 rs587777438

ClinVar genetic disease variations for Hyperaldosteronism, Familial, Type Iii:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 KCNJ5 NM_000890.4(KCNJ5): c.472A> G (p.Thr158Ala) single nucleotide variant Pathogenic rs387906778 GRCh37 Chromosome 11, 128781640: 128781640
2 KCNJ5 NM_000890.4(KCNJ5): c.472A> G (p.Thr158Ala) single nucleotide variant Pathogenic rs387906778 GRCh38 Chromosome 11, 128911745: 128911745
3 KCNJ5 NM_000890.3(KCNJ5): c.451G> A (p.Gly151Arg) single nucleotide variant Pathogenic/Likely pathogenic rs386352319 GRCh37 Chromosome 11, 128781619: 128781619
4 KCNJ5 NM_000890.3(KCNJ5): c.451G> A (p.Gly151Arg) single nucleotide variant Pathogenic/Likely pathogenic rs386352319 GRCh38 Chromosome 11, 128911724: 128911724
5 KCNJ5 NM_000890.4(KCNJ5): c.452G> A (p.Gly151Glu) single nucleotide variant Pathogenic rs587777437 GRCh38 Chromosome 11, 128911725: 128911725
6 KCNJ5 NM_000890.4(KCNJ5): c.452G> A (p.Gly151Glu) single nucleotide variant Pathogenic rs587777437 GRCh37 Chromosome 11, 128781620: 128781620
7 KCNJ5 NM_000890.4(KCNJ5): c.470T> G (p.Ile157Ser) single nucleotide variant Pathogenic rs587777438 GRCh38 Chromosome 11, 128911743: 128911743
8 KCNJ5 NM_000890.4(KCNJ5): c.470T> G (p.Ile157Ser) single nucleotide variant Pathogenic rs587777438 GRCh37 Chromosome 11, 128781638: 128781638
9 KCNJ5 NM_000890.4(KCNJ5): c.736G> A (p.Glu246Lys) single nucleotide variant Pathogenic rs587777439 GRCh38 Chromosome 11, 128912009: 128912009
10 KCNJ5 NM_000890.4(KCNJ5): c.736G> A (p.Glu246Lys) single nucleotide variant Pathogenic rs587777439 GRCh37 Chromosome 11, 128781904: 128781904

Expression for Hyperaldosteronism, Familial, Type Iii

Search GEO for disease gene expression data for Hyperaldosteronism, Familial, Type Iii.

Pathways for Hyperaldosteronism, Familial, Type Iii

GO Terms for Hyperaldosteronism, Familial, Type Iii

Sources for Hyperaldosteronism, Familial, Type Iii

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74 UMLS via Orphanet
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