A Novel Case of Somatic KCNJ5 Mutation in Pediatric-Onset Aldosterone-Producing Adenoma

Abstract

Aldosterone-producing adenoma (APA), a subtype of primary aldosteronism, is a common cause of secondary hypertension in adults. Somatic KCNJ5 mutations have been identified in about 12%–80% of adult-onset APA. In contrast, there has been no previous reported case of pediatric-onset APA in whom a somatic KCNJ5 mutation was confirmed.We report an 11-year-old Japanese girl who had experienced recurrent headaches and nausea for more than 2 years before hypertension was observed (blood pressure, 150/82 mm Hg). Plasma renin activity was <0.1 ng/mL per hour even after a captopril-challenge or upright furosemide-loading test. Plasma aldosterone concentrations (PACs) before and after saline-infusion test were 28.0 and 40.6 ng/dL, respectively. Plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels were 16.5 pg/mL and 16.7 µg/dL, respectively. The patient was diagnosed with APA in the left adrenal gland on the basis of selective adrenal venous sampling after ACTH stimulation (PAC in the left adrenal vein, 3630 ng/dL) and histopathologic findings of the tumor obtained by laparoscopic left adrenalectomy. Sanger sequencing of KCNJ5 using genomic DNA from peripheral lymphocytes and laser-captured microdissected APA tissues demonstrated the presence of a somatic KCNJ5 mutation p.L168R, previously reported only in adult-onset APA. Immunohistochemistry detected strong immunoreactivity for CYP11B2, but not for CYP11B1 in the APA, consistent with the endocrinologic findings in this patient.Somatic KCNJ5 mutations are also identified in pediatric-onset APA. Further cases are needed to elucidate functional characteristics of pediatric-onset APA with a somatic KCNJ5 mutation.

Expression of aldosterone synthase CYP11B2 was inversely correlated with longevity

“…Adrenal samples from autopsy cases were retrospectively selected for analyses; histological and immunohistochemical staining was performed as previously reported (see images of all samples in Supplemental Fig. 1) [9,10,23]; low-quality samples were excluded (see 'Sample selection' in the Materials and Methods and Supplemental Fig. 2A-D).…”

Primary aldosteronism caused by a pI157S somatic KCNJ5 mutation in a black adolescent female with aldosterone-producing adenoma

“…Two forms of PA are the most common presentations: namely aldosterone-producing adenomas (APA) accounting for 30-70% of patients and bilateral zona idiopathic hyperaldosteronism (IAH also accounting for 30-70% of patients with rare cases of unilateral hyperplasia, aldosterone-producing carcinomas and familial hyperaldosteronism accounting for 1-2% (1). Sporadic cases of PA are rare in the pediatric population (3)(4)(5). Only a limited number of cases have been reported in the pediatric literature, most of which have been of the familial type 3 (5)(6)(7) or presenting with a mosaicism (8) all bearing a mutation of the potassium voltage-gated channel subfamily J member 5 gene (KCNJ5).…”

“…Only a limited number of cases have been reported in the pediatric literature, most of which have been of the familial type 3 (5)(6)(7) or presenting with a mosaicism (8) all bearing a mutation of the potassium voltage-gated channel subfamily J member 5 gene (KCNJ5). A somatic mutation of the KCNJ5 gene mutated at p.L168R was first described in a child with moderate to severe hypertension and hypokalemia and low renin with high aldosterone levels by Uchida et al (3). In addition to mutations of the KCNJ5 channel, calcium (CACNA1D and CACNA1H) and chloride (CLCN2) channel gene mutations have been reported in adults and in familial cases and somatic mutations of the sodium ATPase pump (ATP1A1) and calcium pump (ATP2A3) mutations in adults have been described (9)(10)(11)(12).…”

“…A somatic mutation of the KCNJ5 gene mutated at p.L168R was first described in a child with moderate to severe hypertension and hypokalemia and low renin with high aldosterone levels by Uchida et al. ( 3 ). In addition to mutations of the KCNJ5 channel, calcium ( CACNA1D and CACNA1H ) and chloride ( CLCN2 ) channel gene mutations have been reported in adults and in familial cases and somatic mutations of the sodium ATPase pump ( ATP1A1 ) and calcium pump ( ATP2A3 ) mutations in adults have been described ( 9 – 12 ).…”