Pseudohypoaldosteronism in a neonate presenting as life-threatening arrhythmia

Rajpoot, Sudeep K; Maggi, Carlos; Bhangoo, Amrit

doi:10.1530/edm-13-0077

Cited by 16 publications

(10 citation statements)

References 16 publications

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“…Hyperkalemia in patients with PHA-I is life-threatening, leading to cardiac arrhythmia and, ultimately, to cardiac arrest. 22,23 Our data reveal a severe hyperkalemia accompanied by a decrease in food intake and a severe dehydration. Values are given as mean6SEM; number of mice is indicated in parentheses.…”

Section: Deletion Of Genac Subunits In Adult Nephrons Leads To Severementioning

confidence: 61%

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout

Boscardin

Perrier

Sergi

et al. 2018

JASN

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The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide-sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and potassium and colocalize in the late distal convoluted tubule of the kidney. Loss of the ENaC subunit leads to a perinatal lethal phenotype characterized by sodium loss and hyperkalemia resembling the human syndrome pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific deletion ofENaC in mice mimics the lethal phenotype observed in neonates, and as in humans, this phenotype is prevented by a high sodium (HNa)/low potassium (LK) rescue diet. Rescue reflects activation of NCC, which is suppressed at baseline by elevated plasma potassium concentration. In this study, we investigated the role of the ENaC subunit in the PHA-I phenotype. Nephron-specificENaC knockout mice also presented with salt-wasting syndrome and severe hyperkalemia. Unlike mice lacking ENaC orΕΝaC, an HNa/LK diet did not normalize plasma potassium (K) concentration or increase NCC activation. However, when K was eliminated from the diet at the time that ENaC was deleted, plasma K concentration and NCC activity remained normal, and progressive weight loss was prevented. Loss of the late distal convoluted tubule, as well as overall reduced ENaC subunit expression, may be responsible for the more severe hyperkalemia. We conclude that plasma K concentration becomes the determining and limiting factor in regulating NCC activity, regardless of Na balance in ENaC-deficient mice.

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Section: Deletion Of Genac Subunits In Adult Nephrons Leads To Severementioning

confidence: 61%

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout

Boscardin

Perrier

Sergi

et al. 2018

JASN

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“…Although fortunately not present in our patient, severe hyperkalemia may manifest with a range of clinical signs, from weakness or flaccid paralysis (9) to severe arrhythmias (10). PHA1 due to mutations in ENaC affects a range of organ systems; patients may also present with skin and pulmonary infections or severe diarrhea (11). PHA1 due to mutation in the NR3C2 gene, encoding the mineralocorticoid receptor, is a milder disease affecting only the kidneys, with symptoms generally resolving in infancy (12).…”

Section: Discussionmentioning

confidence: 69%

Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene

Nobel

Lodish

Raygada

et al. 2016

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryAutosomal recessive pseudohypoaldosteronism type 1 (PHA1) is a rare disorder characterized by sodium wasting, failure to thrive, hyperkalemia, hypovolemia and metabolic acidosis. It is due to mutations in the amiloride-sensitive epithelial sodium channel (ENaC) and is characterized by diminished response to aldosterone. Patients may present with life-threatening hyperkalemia, which must be recognized and appropriately treated. A 32-year-old female was referred to the National Institutes of Health (NIH) for evaluation of hyperkalemia and muscle pain. Her condition started in the second week of life, when she was brought to an outside hospital lethargic and unresponsive. At that time, she was hypovolemic, hyperkalemic and acidotic, and was eventually treated with sodium bicarbonate and potassium chelation. At the time of the presentation to the NIH, her laboratory evaluation revealed serum potassium 5.1 mmol/l (reference range: 3.4–5.1 mmol/l), aldosterone 2800 ng/dl (reference range: ≤21 ng/dl) and plasma renin activity 90 ng/ml/h (reference range: 0.6–4.3 ng/ml per h). Diagnosis of PHA1 was suspected. Sequencing of the SCNN1B gene, which codes for ENaC, revealed that the patient is a compound heterozygote for two novel variants (c.1288delC and c.1466+1 G>A), confirming the suspected diagnosis of PHA1. In conclusion, we report a patient with novel variants of the SCNN1B gene causing PHA1 with persistent, symptomatic hyperkalemia.Learning points PHA1 is a rare genetic condition, causing functional abnormalities of the amiloride-sensitive ENaC.PHA1 was caused by previously unreported SCNN1B gene mutations (c.1288delC and c.1466+1 G>A).Early recognition of this condition and adherence to symptomatic therapy is important, as the electrolyte abnormalities found may lead to severe dehydration, cardiac arrhythmias and even death.High doses of sodium polystyrene sulfonate, sodium chloride and sodium bicarbonate are required for symptomatic treatment.

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“…To vodi do povečanega izločanja natrija in vode ter do zmanjšanega izločanja kalija kljub relativno visokim vrednostim renina in aldosterona v plazmi (3,4). V stresnih razmerah se stanje lahko hitro poslabša, kar privede do dehidracije, šoka, metabolne acidoze ter hiperkaliemije z nevarnimi aritmijami (5).…”

Section: Uvodunclassified

“…Bolniki imajo zato hiponatremič-no dehidracijo, hiperkaliemijo ter metabolno acidozo, vrednosti renina in aldosterona v serumu pa sta povišani. Edino učinkovito zdravljenje je nadomeščanje tekočin in postopna poprava elektrolitov (5,6,(8)(9).…”

Section: Uvodunclassified

Sekundarni psevdohipoaldosteronizem pri novorojenčku z akutnim vnetjem sečil – Prikaz primera

2017

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IzvlečekHiponatremija in hiperkaliemija lahko pomenita pri novorojenčku življenje ogrožujoče stanje, pri katerem največkrat pomislimo na bolezni nadledvične žleze, zlasti na prirojeno hiperplazijo. Redkejše pa so motnje v odzivnosti ledvičnih celic na aldosteron, kar imenujemo psevdohipoaldosteronizem. Sekundarni psevdohipoaldosteronizem je malokrat opisana, prehodna motnja v elektrolitskem ravnovesju, ki nastane zaradi neodzivnosti tubularnih celic na aldosteron pri novorojenčku in malem dojenčku s prirojenimi okvarami sečil in/ali hudim vnetjem.V članku predstavljamo primer 4-tedenskega novorojenčka s hudo dehidracijo, hiponatremijo in hiperkaliemijo ter povišanimi vrednostmi aldosterona ob prebolevanju akutnega pielonefritisa. Otrok ni imel značilnih kliničnih znakov za okužbo sečil. Po nadomeščanju tekočin, elektrolitov in zdravljenju okužbe, se mu je stanje povsem popravilo. S kasnejšimi slikovnimi preiskavami razvojnih nepravilnosti sečil nismo dokazali. Glede na potek bolezni in podatke iz literature sklepamo, da je elektrolitsko neravnovesje povzročila prehodna rezistentnost vnetih celic distalnega tubula na aldosteron. AbstractHiponatremia and hyperkalemia in a newborn can be a life threatening disorder caused by different diseases, including congenital adrenal hyperplasia, or less freqently by a genetical or acquired tubular cell resistance to aldosteron, called pseudohypoaldosteronism. Secondary pseudohypoaldosteronism is a rare, reversible electrolyte disorder caused by aldosterone resistance in infants with congenital urinary tract malformations and/or urinary tract infection.We present a 4-week-old boy with severe hyponatremia, hyperkalemia and elevated aldosterone levels during an episode of pyelonephritis. The disorder improved completely with antibiotic treatment, rehydration and electrolyte correction. Further investigations showed no structural urinary tract anomalies. According to the literature, we concluded that electrolyte disturbances were caused by aldosterone resistance of the inflamed tubular cels and subsequent defective transepithelial sodium transport. UvodAldosteron je steroidni hormon nadledvične žleze, ki primarno deluje na celice v zbiralnem tubulu ledvic. Preko sistema renin-angiotenzin-aldosteron

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Pseudohypoaldosteronism in a neonate presenting as life-threatening arrhythmia

Cited by 16 publications

References 16 publications

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout

Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific γENaC Knockout

Pseudohypoaldosteronism type 1 due to novel variants of SCNN1B gene

Sekundarni psevdohipoaldosteronizem pri novorojenčku z akutnim vnetjem sečil – Prikaz primera

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