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Familial hyperaldosteronism type III a novel case and review of literature

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Abstract

Less than 15% of hypertension cases in children are secondary to a primary hyperaldosteronism. This is idiopathic in 60% of the cases, secondary to a unilateral adenoma in 30% and 10% remaining by primary adrenal hyperplasia, familial hyperaldosteronism, ectopic aldosterone production or adrenocortical carcinoma.To date, four types of familial hyperaldosteronism (FH I to FH IV) have been reported. FH III is caused by germline mutations in KCNJ5, encoding the potassium channel Kir3.4. The mutations cause the channel to lose its selectivity for potassium, allowing large quantities of sodium to enter the cell. As a consequence, the membrane depolarizes, voltage-gated calcium channels open, calcium enters the cell, initiating the cascade that leads to aldosterone synthesis. Somatic mutations in KCNJ5 has also been described in aldosterone-producing adenomas. The most frequent presentation of FH III is with severe hyperaldosteronism symptoms and resistance to pharmacological therapy which leads to bilateral adrenalectomy. We will review current literature and describe a child with FH III due to a novel de novo deletion in KCNJ5 with wild phenotype as a sign of clinical variability of this disease.

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Abbreviations

FH:

Familial hyperaldosteronism

PA:

Primary aldosteronism

APA:

Aldosterone producing adenoma

BAH:

Bilateral adrenal hyperplasia

ACTH:

Adrenocorticotropic hormone

BP:

Blood pressure

SDS:

Standard deviation

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Authors and Affiliations

  1. Department of Pediatrics, Hospital Lluís Alcanyís de Xàtiva, Ctra. Xàtiva a Silla km 2, 46800, Xàtiva, Valencia, Spain

    Natividad Pons Fernández, Julia Morata, Ana Moriano & Fernando Calvo

  2. Hospital Universitario y Politécnico la Fe de Valencia, Valencia, Spain

    Francisca Moreno, Sara León, Carmen De Mingo & Ángel Zuñiga

Authors
  1. Natividad Pons Fernández
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  2. Francisca Moreno
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  3. Julia Morata
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  4. Ana Moriano
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  5. Sara León
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  6. Carmen De Mingo
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  7. Ángel Zuñiga
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  8. Fernando Calvo
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Contributions

Dr. Pons conceptualized the review, drafted the initial manuscript, and approved the final manuscript as submitted. Drs Moreno, Morata, Moriano, León, de Mingo and Calvo carried out the initial analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. Dr. Zuñiga carried out the genetic test and approved the final manuscript.

Corresponding author

Correspondence to Natividad Pons Fernández.

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Dr. Pons and the remaining authors have no financial relationships relevant to this article to disclose.

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Dr. Pons and the other authors have no conflicts of interest to disclose.

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Pons Fernández, N., Moreno, F., Morata, J. et al. Familial hyperaldosteronism type III a novel case and review of literature. Rev Endocr Metab Disord 20, 27–36 (2019). https://doi.org/10.1007/s11154-018-9481-0

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