MCID: PSD114
MIFTS: 46

Pseudohypoaldosteronism, Type I, Autosomal Recessive

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

Aliases & Classifications for Pseudohypoaldosteronism, Type I, Autosomal Recessive

MalaCards integrated aliases for Pseudohypoaldosteronism, Type I, Autosomal Recessive:

Name: Pseudohypoaldosteronism, Type I, Autosomal Recessive 57 73
Autosomal Recessive Pseudohypoaldosteronism Type 1 12 53 59 15
Pseudohypoaldosteronism Type 1 Autosomal Recessive 53 29 6 40
Pha1b 57 12 53 75
Pseudohypoaldosteronism, Type I 57 13 73
Pseudohypoaldosteronism Type 1 25 59 29
Generalized Pseudohypoaldosteronism Type 1 53 59
Pseudohypoaldosteronism 44 73
Pseudohypoaldosteronism Type I, Autosomal Recessive 75
Pseudohypoaldosteronism 1, Autosomal Recessive 75
Pseudohypoaldosteronism, Type I, Recessive 6
Pseudohypoaldosteronism Type 1, Recessive 53
Multisystem Pseudohypoaldosteronism 75
Pha Type I, Autosomal Recessive 75
Pseudohypoaldosteronism Type I 25
Pha I, Autosomal Recessive 57
Autosomal Recessive Pha 1 12
Generalized Pha1 53
Pha Type 1 59
Pha1 25

Characteristics:

Orphanet epidemiological data:

59
generalized pseudohypoaldosteronism type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;
pseudohypoaldosteronism type 1
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
favorable response to sodium chloride treatment
may be lethal in the neonatal period


HPO:

32
pseudohypoaldosteronism, type i, autosomal recessive:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare renal diseases


External Ids:

OMIM 57 264350
Disease Ontology 12 DOID:0060854
ICD10 33 N25.8
MeSH 44 D011546
UMLS via Orphanet 74 C1449843 C0268436
ICD10 via Orphanet 34 N25.8
MESH via Orphanet 45 D011546
MedGen 42 C1449843
UMLS 73 C0268436

Summaries for Pseudohypoaldosteronism, Type I, Autosomal Recessive

OMIM : 57 Autosomal recessive pseudohypoaldosteronism type I is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Laboratory evaluation shows hyponatremia, hyperkalemia, and increased plasma renin activity with high serum aldosterone concentrations. Respiratory tract infections are common in affected children and may be mistaken for cystic fibrosis (CF; 219700). Aggressive salt replacement and control of hyperkalemia results in survival, and the disorder appears to become less severe with age (review by Scheinman et al., 1999). A milder, autosomal dominant form of type I pseudohypoaldosteronism (PHA1A; 177735) is caused by mutations in the mineralocorticoid receptor gene (MCR, NR3C2; 600983). Gitelman syndrome (263800), another example of primary renal tubular salt wasting, is due to mutation in the thiazide-sensitive sodium-chloride cotransporter (SLC12A3; 600968). Hanukoglu and Hanukoglu (2016) provided a detailed review of the ENaC gene family, including structure, function, tissue distribution, and associated inherited diseases. (264350)

MalaCards based summary : Pseudohypoaldosteronism, Type I, Autosomal Recessive, also known as autosomal recessive pseudohypoaldosteronism type 1, is related to pseudohypoaldosteronism, type i, autosomal dominant and pseudohypoaldosteronism, and has symptoms including diarrhea and vomiting. An important gene associated with Pseudohypoaldosteronism, Type I, Autosomal Recessive is SCNN1B (Sodium Channel Epithelial 1 Beta Subunit), and among its related pathways/superpathways are Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds and G-Beta Gamma Signaling. Affiliated tissues include kidney, colon and testes, and related phenotypes are failure to thrive and hypotension

Disease Ontology : 12 A pseudohypoaldosteronism characterized by enal salt wasting and high concentrations of sodium in sweat, stool, and saliva that has material basis in homozygous or compound heterozygous mutation in any one of 3 genes encoding subunits of the epithelial sodium channel (ENaC)

Genetics Home Reference : 25 Pseudohypoaldosteronism type 1 (PHA1) is a condition characterized by problems regulating the amount of sodium in the body. Sodium regulation, which is important for blood pressure and fluid balance, primarily occurs in the kidneys. However, sodium can also be removed from the body through other tissues, such as the sweat glands and colon. Pseudohypoaldosteronism type 1 is named for its characteristic signs and symptoms, which mimic (pseudo) low levels (hypo) of a hormone called aldosterone that helps regulate sodium levels. However, people with PHA1 have high levels of aldosterone.

NIH Rare Diseases : 53 Autosomal recessive pseudohypoaldosteronism type 1 is a disorder of electrolyte metabolism characterized by excess loss of salt in the urine and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially dangerous in the newborn period. Laboratory tests may show hyponatremia, hyperkalemia, and increased plasma renin activity with high levels of aldosterone in the blood. Respiratory tract infections are common in affected children. Treatment involves aggressive salt replacement and control of hyperkalemia. The disorder may become less severe with age. Autosomal recessive pseudohypoaldosteronism type 1 (PHA1B) is transmitted in an autosomal recessive manner and is caused by mutations in the genes coding for the subunits of the amiloride-sensitive sodium channel (SCNN1A, SCNN1B and SCNN1G).

UniProtKB/Swiss-Prot : 75 Pseudohypoaldosteronism 1, autosomal recessive: A rare salt wasting disease resulting from target organ unresponsiveness to mineralocorticoids. PHA1B is a severe form involving multiple organ systems, and characterized by an often fulminant presentation in the neonatal period with dehydration, hyponatremia, hyperkalemia, metabolic acidosis, failure to thrive and weight loss.

Related Diseases for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Graphical network of the top 20 diseases related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:



Diseases related to Pseudohypoaldosteronism, Type I, Autosomal Recessive

Symptoms & Phenotypes for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Metabolic Features:
dehydration
metabolic acidosis

Laboratory Abnormalities:
hyponatremia
hyperkalemia
increased serum aldosterone
increased plasma renin activity
markedly elevated sodium in urine, sweat, saliva, and stool

Respiratory:
recurrent respiratory infections

Abdomen Gastrointestinal:
vomiting
diarrhea
poor feeding

Genitourinary Kidneys:
renal salt wasting


Clinical features from OMIM:

264350

Human phenotypes related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

32 (show all 14)
# Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 hypotension 32 HP:0002615
3 recurrent respiratory infections 32 HP:0002205
4 feeding difficulties in infancy 32 HP:0008872
5 dehydration 32 HP:0001944
6 vomiting 32 HP:0002013
7 hyperaldosteronism 32 HP:0000859
8 hyponatremia 32 HP:0002902
9 diarrhea 32 HP:0002014
10 metabolic acidosis 32 HP:0001942
11 renal salt wasting 32 HP:0000127
12 hyperkalemia 32 HP:0002153
13 hyperactive renin-angiotensin system 32 HP:0000841
14 pseudohypoaldosteronism 32 HP:0008242

UMLS symptoms related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:


diarrhea, vomiting

MGI Mouse Phenotypes related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.7 ASIC2 ATP6V1B1 LOX NR3C2 REN SCNN1A
2 homeostasis/metabolism MP:0005376 9.5 ATP6V1B1 LOX NR3C2 REN SCNN1A SCNN1B
3 renal/urinary system MP:0005367 9.1 ATP6V1B1 NR3C2 REN SCNN1A SCNN1B SCNN1G

Drugs & Therapeutics for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Cochrane evidence based reviews: pseudohypoaldosteronism

Genetic Tests for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Genetic tests related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Pseudohypoaldosteronism Type 1 Autosomal Recessive 29 SCNN1A SCNN1B SCNN1G
2 Pseudohypoaldosteronism Type 1 29

Anatomical Context for Pseudohypoaldosteronism, Type I, Autosomal Recessive

MalaCards organs/tissues related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

41
Kidney, Colon, Testes

Publications for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Articles related to Pseudohypoaldosteronism, Type I, Autosomal Recessive:

# Title Authors Year
1
Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1. ( 23416952 )
2013
2
Disorders of the epithelial Na(+) channel in Liddle's syndrome and autosomal recessive pseudohypoaldosteronism type 1. ( 11014928 )
2000
3
Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis. ( 7593448 )
1995

Variations for Pseudohypoaldosteronism, Type I, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Pseudohypoaldosteronism, Type I, Autosomal Recessive:

75
# Symbol AA change Variation ID SNP ID
1 SCNN1A p.Ser562Leu VAR_015834 rs137852635
2 SCNN1A p.Gly327Cys VAR_026518 rs974854786
3 SCNN1B p.Gly37Ser VAR_007127 rs137852706

ClinVar genetic disease variations for Pseudohypoaldosteronism, Type I, Autosomal Recessive:

6
(show top 50) (show all 298)
# Gene Variation Type Significance SNP ID Assembly Location
1 SCNN1G SCNN1G, IVS11, G-A, -1 single nucleotide variant Pathogenic
2 SCNN1G SCNN1G, IVSAAS, G-A, -1 single nucleotide variant Pathogenic
3 SCNN1G SCNN1G, 1-BP DEL, 1627G deletion Pathogenic
4 SCNN1B NM_000336.2(SCNN1B): c.109G> A (p.Gly37Ser) single nucleotide variant Pathogenic rs137852706 GRCh37 Chromosome 16, 23360029: 23360029
5 SCNN1B NM_000336.2(SCNN1B): c.109G> A (p.Gly37Ser) single nucleotide variant Pathogenic rs137852706 GRCh38 Chromosome 16, 23348708: 23348708
6 SCNN1A SCNN1A, 2-BP DEL, FS144TER deletion Pathogenic
7 SCNN1A NM_001038.5(SCNN1A): c.1522C> T (p.Arg508Ter) single nucleotide variant Pathogenic rs137852634 GRCh37 Chromosome 12, 6458147: 6458147
8 SCNN1A NM_001038.5(SCNN1A): c.1522C> T (p.Arg508Ter) single nucleotide variant Pathogenic rs137852634 GRCh38 Chromosome 12, 6348981: 6348981
9 SCNN1A SCNN1A, 1-BP DEL, 1449C deletion Pathogenic
10 SCNN1A SCNN1A, 1-BP DEL, 729A deletion Pathogenic
11 SCNN1A NM_001038.5(SCNN1A): c.1685C> T (p.Ser562Leu) single nucleotide variant Pathogenic rs137852635 GRCh37 Chromosome 12, 6457364: 6457364
12 SCNN1A NM_001038.5(SCNN1A): c.1685C> T (p.Ser562Leu) single nucleotide variant Pathogenic rs137852635 GRCh38 Chromosome 12, 6348198: 6348198
13 SCNN1A NM_001038.5(SCNN1A): c.1000G> A (p.Ala334Thr) single nucleotide variant Benign rs11542844 GRCh37 Chromosome 12, 6464581: 6464581
14 SCNN1A NM_001038.5(SCNN1A): c.1000G> A (p.Ala334Thr) single nucleotide variant Benign rs11542844 GRCh38 Chromosome 12, 6355415: 6355415
15 SCNN1A NM_001038.5(SCNN1A): c.1987A> G (p.Thr663Ala) single nucleotide variant Benign rs2228576 GRCh37 Chromosome 12, 6457062: 6457062
16 SCNN1A NM_001038.5(SCNN1A): c.1987A> G (p.Thr663Ala) single nucleotide variant Benign rs2228576 GRCh38 Chromosome 12, 6347896: 6347896
17 SCNN1G NM_001039.3(SCNN1G): c.474T> C (p.Ile158=) single nucleotide variant Benign rs5735 GRCh37 Chromosome 16, 23200848: 23200848
18 SCNN1G NM_001039.3(SCNN1G): c.474T> C (p.Ile158=) single nucleotide variant Benign rs5735 GRCh38 Chromosome 16, 23189527: 23189527
19 SCNN1G NM_001039.3(SCNN1G): c.636C> T (p.Ser212=) single nucleotide variant Benign/Likely benign rs5739 GRCh37 Chromosome 16, 23203690: 23203690
20 SCNN1G NM_001039.3(SCNN1G): c.636C> T (p.Ser212=) single nucleotide variant Benign/Likely benign rs5739 GRCh38 Chromosome 16, 23192369: 23192369
21 SCNN1G NM_001039.3(SCNN1G): c.1176+14A> G single nucleotide variant Benign rs5740 GRCh37 Chromosome 16, 23221183: 23221183
22 SCNN1G NM_001039.3(SCNN1G): c.1176+14A> G single nucleotide variant Benign rs5740 GRCh38 Chromosome 16, 23209862: 23209862
23 SCNN1G NM_001039.3(SCNN1G): c.1947C> G (p.Leu649=) single nucleotide variant Benign rs5723 GRCh37 Chromosome 16, 23226787: 23226787
24 SCNN1G NM_001039.3(SCNN1G): c.1947C> G (p.Leu649=) single nucleotide variant Benign rs5723 GRCh38 Chromosome 16, 23215466: 23215466
25 SCNN1B NM_000336.2(SCNN1B): c.279T> C (p.Pro93=) single nucleotide variant Benign rs238547 GRCh37 Chromosome 16, 23360199: 23360199
26 SCNN1B NM_000336.2(SCNN1B): c.279T> C (p.Pro93=) single nucleotide variant Benign rs238547 GRCh38 Chromosome 16, 23348878: 23348878
27 SCNN1B NM_000336.2(SCNN1B): c.1221A> G (p.Pro407=) single nucleotide variant Likely benign rs2303156 GRCh37 Chromosome 16, 23387127: 23387127
28 SCNN1B NM_000336.2(SCNN1B): c.1221A> G (p.Pro407=) single nucleotide variant Likely benign rs2303156 GRCh38 Chromosome 16, 23375806: 23375806
29 SCNN1B NM_000336.2(SCNN1B): c.1325G> T (p.Gly442Val) single nucleotide variant Benign rs1799980 GRCh37 Chromosome 16, 23388540: 23388540
30 SCNN1B NM_000336.2(SCNN1B): c.1325G> T (p.Gly442Val) single nucleotide variant Benign rs1799980 GRCh38 Chromosome 16, 23377219: 23377219
31 SCNN1B NM_000336.2(SCNN1B): c.1467-14G> A single nucleotide variant Benign rs34618783 GRCh37 Chromosome 16, 23391401: 23391401
32 SCNN1B NM_000336.2(SCNN1B): c.1467-14G> A single nucleotide variant Benign rs34618783 GRCh38 Chromosome 16, 23380080: 23380080
33 SCNN1G NM_001039.3(SCNN1G): c.387T> C (p.Tyr129=) single nucleotide variant Benign rs5734 GRCh37 Chromosome 16, 23200761: 23200761
34 SCNN1G NM_001039.3(SCNN1G): c.387T> C (p.Tyr129=) single nucleotide variant Benign rs5734 GRCh38 Chromosome 16, 23189440: 23189440
35 SCNN1G NM_001039.3(SCNN1G): c.549C> T (p.Gly183=) single nucleotide variant Benign rs5737 GRCh37 Chromosome 16, 23200923: 23200923
36 SCNN1G NM_001039.3(SCNN1G): c.549C> T (p.Gly183=) single nucleotide variant Benign rs5737 GRCh38 Chromosome 16, 23189602: 23189602
37 SCNN1G NM_001039.3(SCNN1G): c.1432-7G> A single nucleotide variant Benign rs13306653 GRCh37 Chromosome 16, 23224416: 23224416
38 SCNN1G NM_001039.3(SCNN1G): c.1432-7G> A single nucleotide variant Benign rs13306653 GRCh38 Chromosome 16, 23213095: 23213095
39 SCNN1B NM_000336.2(SCNN1B): c.879C> T (p.Phe293=) single nucleotide variant Benign rs250563 GRCh37 Chromosome 16, 23379279: 23379279
40 SCNN1B NM_000336.2(SCNN1B): c.879C> T (p.Phe293=) single nucleotide variant Benign rs250563 GRCh38 Chromosome 16, 23367958: 23367958
41 SCNN1B NM_000336.2(SCNN1B): c.1401C> T (p.Ser467=) single nucleotide variant Benign/Likely benign rs74012901 GRCh37 Chromosome 16, 23388704: 23388704
42 SCNN1B NM_000336.2(SCNN1B): c.1401C> T (p.Ser467=) single nucleotide variant Benign/Likely benign rs74012901 GRCh38 Chromosome 16, 23377383: 23377383
43 SCNN1B NM_000336.2(SCNN1B): c.1765G> A (p.Gly589Ser) single nucleotide variant Likely benign rs61759926 GRCh37 Chromosome 16, 23391964: 23391964
44 SCNN1B NM_000336.2(SCNN1B): c.1765G> A (p.Gly589Ser) single nucleotide variant Likely benign rs61759926 GRCh38 Chromosome 16, 23380643: 23380643
45 SCNN1A NM_001038.5(SCNN1A): c.1853G> T (p.Cys618Phe) single nucleotide variant Benign rs3741913 GRCh37 Chromosome 12, 6457196: 6457196
46 SCNN1A NM_001038.5(SCNN1A): c.1853G> T (p.Cys618Phe) single nucleotide variant Benign rs3741913 GRCh38 Chromosome 12, 6348030: 6348030
47 SCNN1A NM_001038.5(SCNN1A): c.540G> T (p.Leu180=) single nucleotide variant Benign/Likely benign rs55859427 GRCh37 Chromosome 12, 6472753: 6472753
48 SCNN1A NM_001038.5(SCNN1A): c.540G> T (p.Leu180=) single nucleotide variant Benign/Likely benign rs55859427 GRCh38 Chromosome 12, 6363587: 6363587
49 SCNN1A NM_001038.5(SCNN1A): c.541C> T (p.Arg181Trp) single nucleotide variant Benign/Likely benign rs55797039 GRCh37 Chromosome 12, 6472752: 6472752
50 SCNN1A NM_001038.5(SCNN1A): c.541C> T (p.Arg181Trp) single nucleotide variant Benign/Likely benign rs55797039 GRCh38 Chromosome 12, 6363586: 6363586

Expression for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Search GEO for disease gene expression data for Pseudohypoaldosteronism, Type I, Autosomal Recessive.

Pathways for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Pathways related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.01 ASIC2 ATP6V1B1 SCNN1A SCNN1B SCNN1D SCNN1G
2
Show member pathways
12.63 SCNN1A SCNN1B SCNN1D SCNN1G
3
Show member pathways
12.32 SCNN1A SCNN1B SCNN1D SCNN1G
4
Show member pathways
11.93 ASIC2 ATP6V1B1 SCNN1A SCNN1B SCNN1D SCNN1G
5
Show member pathways
11.71 ASIC2 SCNN1A SCNN1B SCNN1G
6
Show member pathways
11.38 NR3C2 REN
7 11.13 NR3C2 SCNN1A SCNN1B SCNN1G
8 11.01 SCNN1A SCNN1B SCNN1G
9 11 SCNN1A SCNN1B SCNN1D SCNN1G
10 10.04 SCNN1A SCNN1B SCNN1D SCNN1G

GO Terms for Pseudohypoaldosteronism, Type I, Autosomal Recessive

Cellular components related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apical plasma membrane GO:0016324 9.26 ATP6V1B1 SCNN1A SCNN1B SCNN1G
2 sodium channel complex GO:0034706 8.8 SCNN1A SCNN1B SCNN1G

Biological processes related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.88 ASIC2 ATP6V1B1 SCNN1A SCNN1B SCNN1D SCNN1G
2 response to stimulus GO:0050896 9.76 SCNN1A SCNN1B SCNN1D SCNN1G
3 excretion GO:0007588 9.61 ATP6V1B1 SCNN1B SCNN1G
4 sensory perception of taste GO:0050909 9.56 SCNN1A SCNN1B SCNN1D SCNN1G
5 sodium ion transport GO:0006814 9.55 ASIC2 SCNN1A SCNN1B SCNN1D SCNN1G
6 sodium ion homeostasis GO:0055078 9.54 SCNN1A SCNN1B SCNN1G
7 multicellular organismal water homeostasis GO:0050891 9.5 SCNN1A SCNN1B SCNN1G
8 ion transmembrane transport GO:0034220 9.43 ASIC2 ATP6V1B1 SCNN1A SCNN1B SCNN1D SCNN1G
9 sodium ion transmembrane transport GO:0035725 9.02 ASIC2 SCNN1A SCNN1B SCNN1D SCNN1G

Molecular functions related to Pseudohypoaldosteronism, Type I, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 WW domain binding GO:0050699 9.33 SCNN1A SCNN1B SCNN1G
2 sodium channel activity GO:0005272 9.13 ASIC2 SCNN1A SCNN1G
3 ligand-gated sodium channel activity GO:0015280 9.02 ASIC2 SCNN1A SCNN1B SCNN1D SCNN1G

Sources for Pseudohypoaldosteronism, Type I, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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