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Autosomal recessive pseudohypoaldosteronism type 1(PHA1B1)

MedGen UID:
1823950
Concept ID:
C5774176
Disease or Syndrome
Synonyms: PHA I, AUTOSOMAL RECESSIVE; PHA1B1; Pseudohypoaldosteronism Type 1, Recessive; Pseudohypoaldosteronism, Type I, Autosomal Recessive; Pseudohypoaldosteronism, Type I, Recessive; PSEUDOHYPOALDOSTERONISM, TYPE IB1, AUTOSOMAL RECESSIVE
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SCNN1A (12p13.31)
 
Monarch Initiative: MONDO:0009917
OMIM®: 264350
Orphanet: ORPHA171876

Definition

Autosomal recessive pseudohypoaldosteronism type I, including PHA1B1, 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. [from OMIM]

Additional description

From MedlinePlus Genetics
The earliest signs of both types of PHA1 are usually the inability to gain weight and grow at the expected rate (failure to thrive) and dehydration, which are typically seen in infants. The characteristic features of both types of PHA1 are excessive amounts of sodium released in the urine (salt wasting), which leads to low levels of sodium in the blood (hyponatremia), and high levels of potassium in the blood (hyperkalemia). Infants with PHA1 can also have high levels of acid in the blood (metabolic acidosis). Hyponatremia, hyperkalemia, or metabolic acidosis can cause nonspecific symptoms such as nausea, vomiting, extreme tiredness (fatigue), and muscle weakness in infants with PHA1.

There are two types of PHA1 distinguished by their severity, the genes involved, and how they are inherited. One type, called autosomal dominant PHA1 (also known as renal PHA1) is characterized by excessive sodium loss from the kidneys. This form of the condition is relatively mild and often improves in early childhood. The other type, called autosomal recessive PHA1 (also known as generalized or systemic PHA1) is characterized by sodium loss from the kidneys and other organs, including the sweat glands, salivary glands, and colon. This type of PHA1 is more severe and does not improve with age.

Infants with autosomal recessive PHA1 can have additional signs and symptoms due to the involvement of multiple organs. Affected individuals may experience episodes of abnormal heartbeat (cardiac arrhythmia) or shock because of the imbalance of salts in the body. They may also have recurrent lung infections or lesions on the skin. Although adults with autosomal recessive PHA1 can have repeated episodes of salt wasting, they do not usually have other signs and symptoms of the condition.

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.  https://medlineplus.gov/genetics/condition/pseudohypoaldosteronism-type-1

Clinical features

From HPO
Renal salt wasting
MedGen UID:
375868
Concept ID:
C1846347
Finding
A high concentration of one or more electrolytes in the urine in the presence of low serum concentrations of the electrolyte(s).
Hypotension
MedGen UID:
5715
Concept ID:
C0020649
Finding
Low Blood Pressure, vascular hypotension.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Dehydration
MedGen UID:
8273
Concept ID:
C0011175
Disease or Syndrome
A condition resulting from the excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
Hyperkalemia
MedGen UID:
5691
Concept ID:
C0020461
Finding
An abnormally increased potassium concentration in the blood.
Hyponatremia
MedGen UID:
6984
Concept ID:
C0020625
Finding
An abnormally decreased sodium concentration in the blood.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
Hyperaldosteronism
MedGen UID:
6960
Concept ID:
C0020428
Disease or Syndrome
Overproduction of the mineralocorticoid aldosterone by the adrenal cortex.
Pseudohypoaldosteronism
MedGen UID:
18721
Concept ID:
C0033805
Disease or Syndrome
A state of renal tubular unresponsiveness or resistance to the action of aldosterone.
Hyperactive renin-angiotensin system
MedGen UID:
335401
Concept ID:
C1846345
Finding
An abnormally increased activity of the renin-angiotensin system, causing hypertension by a combination of volume excess and vasoconstrictor mechanisms.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal recessive pseudohypoaldosteronism type 1

Professional guidelines

PubMed

Bandhakavi M, Wanaguru A, Ayuk L, Kirk JM, Barrett TG, Kershaw M, Högler W, Shaw NJ
Eur J Endocrinol 2021 May;184(5):K15-K20. doi: 10.1530/EJE-20-0152. PMID: 33690157

Recent clinical studies

Diagnosis

Huneif MA, Alhazmy ZH, Shoomi AM, Alghofely MA, Heena H, Mushiba AM, AlSaheel A
J Clin Res Pediatr Endocrinol 2022 Jun 7;14(2):244-250. Epub 2021 Apr 8 doi: 10.4274/jcrpe.galenos.2021.2020.0175. PMID: 33829730Free PMC Article
Serra G, Antona V, D'Alessandro MM, Maggio MC, Verde V, Corsello G
Ital J Pediatr 2021 Jun 16;47(1):138. doi: 10.1186/s13052-021-01080-x. PMID: 34134742Free PMC Article
Schweiger B, Moriarty MW, Cadnapaphornchai MA
Curr Opin Pediatr 2009 Apr;21(2):269-71. doi: 10.1097/MOP.0b013e328325a55f. PMID: 19657313

Therapy

Schweiger B, Moriarty MW, Cadnapaphornchai MA
Curr Opin Pediatr 2009 Apr;21(2):269-71. doi: 10.1097/MOP.0b013e328325a55f. PMID: 19657313

Prognosis

Efthymiadou A, Gautschi I, van Bemmelen MX, Sertedaki A, Giannakopoulos A, Chrousos G, Schild L, Chrysis D
Am J Physiol Endocrinol Metab 2023 Jul 1;325(1):E1-E9. Epub 2023 May 3 doi: 10.1152/ajpendo.00332.2022. PMID: 37134141
Huneif MA, Alhazmy ZH, Shoomi AM, Alghofely MA, Heena H, Mushiba AM, AlSaheel A
J Clin Res Pediatr Endocrinol 2022 Jun 7;14(2):244-250. Epub 2021 Apr 8 doi: 10.4274/jcrpe.galenos.2021.2020.0175. PMID: 33829730Free PMC Article
Welzel M, Akin L, Büscher A, Güran T, Hauffa BP, Högler W, Leonards J, Karges B, Kentrup H, Kirel B, Senses EE, Tekin N, Holterhus PM, Riepe FG
Eur J Endocrinol 2013 May;168(5):707-15. Epub 2013 Apr 15 doi: 10.1530/EJE-12-1000. PMID: 23416952

Clinical prediction guides

Welzel M, Akin L, Büscher A, Güran T, Hauffa BP, Högler W, Leonards J, Karges B, Kentrup H, Kirel B, Senses EE, Tekin N, Holterhus PM, Riepe FG
Eur J Endocrinol 2013 May;168(5):707-15. Epub 2013 Apr 15 doi: 10.1530/EJE-12-1000. PMID: 23416952
Schaedel C, Marthinsen L, Kristoffersson AC, Kornfält R, Nilsson KO, Orlenius B, Holmberg L
J Pediatr 1999 Dec;135(6):739-45. doi: 10.1016/s0022-3476(99)70094-6. PMID: 10586178
Chung E, Hanukoglu A, Rees M, Thompson R, Dillon M, Hanukoglu I, Bistritzer T, Kuhnle U, Seckl J, Gardiner RM
J Clin Endocrinol Metab 1995 Nov;80(11):3341-5. doi: 10.1210/jcem.80.11.7593448. PMID: 7593448

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