A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a &lt;i&gt;KLHL3&lt;/i&gt; mutation

Mitani, Marie; Furuichi, Munehiro; Narumi, Shunji; Hasegawa, Tomonobu; Chiga, Motoko; Uchida, Shinichi; Sato, Seiji

doi:10.1297/cpe.25.127

Cited by 7 publications

(7 citation statements)

References 25 publications

(20 reference statements)

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“…Plasma renin activity is low or low-normal and aldosterone concentrations are variable but usually low given the degree of hyperkalemia [ 6 ]. This contrasts with pseudohypoaldosteronism type I, which is associated with aldosterone resistance [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Pseudohypoaldosteronism Type II or Gordon Syndrome: A Rare Syndrome of Hyperkalemia and Hypertension With Normal Renal Function

Manas,

Singh

2024

Cureus

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Pseudohypoaldosteronism type II (PHA II) or Gordon syndrome is characterized by hyperkalemia, hypertension, hyperchloremic metabolic acidosis, low plasma renin activity, and normal kidney function. We report a rare case of a young adult female patient presenting with abdominal pain, diarrhea, and vomiting. She was hypertensive during the presentation. Blood work showed mild anemia, hyperkalemia, hyperchloremia, and metabolic acidosis, with normal renal function and liver function. Plasma renin activity and aldosterone levels were low-normal. These findings were suggestive of PHA II or Gordon syndrome. It is a rare familial disease, with a non-specific presentation and no specific diagnostic criteria, and physicians should suspect it in patients with hyperkalemia in the setting of normal glomerular filtration, along with hypertension (which can be absent), metabolic acidosis, hyperchloremia, low plasma renin activity, and relatively suppressed aldosterone.

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Section: Discussionmentioning

confidence: 99%

Pseudohypoaldosteronism Type II or Gordon Syndrome: A Rare Syndrome of Hyperkalemia and Hypertension With Normal Renal Function

Manas,

Singh

2024

Cureus

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“…It is characterized by hypertension, hyperkalemia, hyperchloremic metabolic acidosis and normal renal function. Plasma renin levels are usually suppressed and aldosterone levels can be variable but are relatively low due to the hyperkalemia ( 20 ). Blood pressure, which may be ignored in children, especially in early infancy, can be an important hint for establishing the diagnosis of PHA2.…”

Section: Discussionmentioning

confidence: 99%

“…The p.T495R residue is located in the fifth Kelch motif of the protein and is involved in substrate binding. The clinical and genetic features of patients with mutations in KLHL3 ( 19 , 20 , 26 – 34 ), including the present study and those who had clinical details published in previous reports, are summarized in Table 3 . Heterozygous mutations are more common than homozygous ones.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone defects in infants and young children with hyperkalemia: A single center retrospective study

et al. 2023

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IntroductionHyperkalemia is a rare but severe condition in young children and usually discovered as a result of hemolysis of the blood samples taken. However, patients with defects in either aldosterone biosynthesis or function can also present with hyperkalemia- as well hyponatremia-associated, and metabolic acidosis. It is a challenge to make an accurate diagnosis of these clinical conditions. We conducted this study to investigate the clinical and genetic features of aldosterone signaling defects associated hyperkalemia in young children.MethodA retrospective review was conducted at the pediatric department of the First Affiliated Hospital of Guangxi Medical University from 2012 to 2022.Results47 patients with hyperkalemia were enrolled, of which 80.9% (n = 38) were diagnosed with primary hypoaldosteronism, including congenital adrenal hyperplasia due to 21-hydroxylase deficiency (n = 32), isolated hypoaldosteronism (n = 1) due to CYP11B2 gene mutation and Xp21 contiguous gene deletion syndrome (n = 1). Additionally, 4 patients were clinically-diagnosed with primary adrenal insufficiency. Nine patients were confirmed with aldosterone resistance, of which one child was diagnosed with pseudohypoaldosteronism (PHA) type 1 with a mutation in the NR3C2 gene and 3 children were identified with PHA type 2 due to novel mutations in either the CUL3 or KLHL3 genes. Five patients had PHA type 3 because of pathologies of either the urinary or intestinal tracts.ConclusionsThe etiologies of infants with hyperkalemia associated with aldosterone defects were mostly due to primary hypoaldosteronism. An elevated plasma aldosterone level may be a useful biomarker for the diagnosis an aldosterone functional defect in patients presented with hyperkalemia. However, a normal plasma aldosterone level does rule out an aldosterone defect in either its biosynthesis or function, especially in young infants. Molecular genetic analyses can greatly help to clarify the complexity of disorders and can be used to confirm the diagnosis.

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“…For instance, one of the South Korean cases of GS caused by the same mutation in the present case (S433N) had a suppressed RAAS (plasma renin activity less than 0.10 ng/mL/h and plasma aldosterone 7.1 ng/dL). Similarly, patients with other sites of KLHL3 mutations (such as Q309R, R528H, H498Y, and L387P) had low plasma renin activity and normal or decreased aldosterone levels [2][3][4][5]. e possible mechanism may be associated with increased NCC activity, which leads to increased NaCl reabsorption and volume-dependent hypertension, thus inhibiting the RAAS (decreased renin activity and aldosterone levels).…”

Section: Discussionmentioning

confidence: 99%

Hypertension Accompanied by Hyperaldosteronism, Hyperkalemia, and Hyperchloremic Acidosis: A Case Report and Literature Review

Yang

Ren

et al. 2020

Case Reports in Endocrinology

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This study reported on a 24-year-old woman who complained of a paroxysmal headache for six months and elevated blood pressure for four months. Laboratory examination revealed increased serum potassium and chloride levels, metabolic acidosis, suppressed renin activity, and increased plasma aldosterone concentration. Whole-exome sequencing revealed a heterozygous mutation in exon 11 of the KLHL3 gene: c.1298G > A. After treatment with low-dose hydrochlorothiazide, her clinical problems were controlled. This patient is the first case of Gordon syndrome (GS) within the Chinese population caused by a heterozygous KLHL3 mutation. A systematic review of the published literature identified 27 patients with GS caused by a KLHL3 mutation. These patients had a mean age of 28.2 ± 22.0 years; 74.1% presented with hypertension, 76.9% with hyperkalemia, and 59.1% with metabolic acidosis. The patients also had varying levels of plasma renin activity and plasma aldosterone concentrations.

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A patient with pseudohypoaldosteronism type II complicated by congenital hypopituitarism carrying a <i>KLHL3</i> mutation

Cited by 7 publications

References 25 publications

Pseudohypoaldosteronism Type II or Gordon Syndrome: A Rare Syndrome of Hyperkalemia and Hypertension With Normal Renal Function

Pseudohypoaldosteronism Type II or Gordon Syndrome: A Rare Syndrome of Hyperkalemia and Hypertension With Normal Renal Function

Aldosterone defects in infants and young children with hyperkalemia: A single center retrospective study

Hypertension Accompanied by Hyperaldosteronism, Hyperkalemia, and Hyperchloremic Acidosis: A Case Report and Literature Review

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