Primary aldosteronism is the most common form of endocrine hypertension. This disorder comprises both sporadic and familial forms. Four familial forms of primary aldosteronism (FH-I to FH-IV) have been described. FH-III is caused by germline mutations in KCNJ5, encoding the potassium channel Kir3.4 (also called GIRK4). These mutations alter the selectivity filter of the channel and lead to abnormal ion currents with loss of potassium selectivity, sodium influx and consequent increased intracellular calcium that causes excessive aldosterone biosynthesis. To date, eleven families have been reported, carrying six different mutations. Although the clinical features are variable, FH-III patients often display severe hyperaldosteronism with an early onset, associated with hypokalemia and diabetes insipidus-like symptoms. In most cases FH-III patients are resistant to pharmacological therapy and require bilateral adrenalectomy to control symptoms. In the present manuscript, we review the genetics and pathological basis of FH-III, the diagnostic work-up, clinical features and therapeutic management. Finally, we will describe a new case of FH-III of an Italian patient carrying a Gly151Arg mutation.Journal of Human Hypertension advance online publication, 27 April 2017; doi:10.1038/jhh.2017.34.

Familial hyperaldosteronism type III

Monticone, S
First
;
Tetti, M;Burrello, J;Buffolo, F;Veglio, F;Williams, TA;Mulatero, P
Last
2017-01-01

Abstract

Primary aldosteronism is the most common form of endocrine hypertension. This disorder comprises both sporadic and familial forms. Four familial forms of primary aldosteronism (FH-I to FH-IV) have been described. FH-III is caused by germline mutations in KCNJ5, encoding the potassium channel Kir3.4 (also called GIRK4). These mutations alter the selectivity filter of the channel and lead to abnormal ion currents with loss of potassium selectivity, sodium influx and consequent increased intracellular calcium that causes excessive aldosterone biosynthesis. To date, eleven families have been reported, carrying six different mutations. Although the clinical features are variable, FH-III patients often display severe hyperaldosteronism with an early onset, associated with hypokalemia and diabetes insipidus-like symptoms. In most cases FH-III patients are resistant to pharmacological therapy and require bilateral adrenalectomy to control symptoms. In the present manuscript, we review the genetics and pathological basis of FH-III, the diagnostic work-up, clinical features and therapeutic management. Finally, we will describe a new case of FH-III of an Italian patient carrying a Gly151Arg mutation.Journal of Human Hypertension advance online publication, 27 April 2017; doi:10.1038/jhh.2017.34.
2017
31
12
776
781
Primary aldosteronism, familial hyperaldosteronism, hypertension
Monticone, S; Tetti, M; Burrello, J; Buffolo, F; De Giovanni, R; Veglio, F; Williams, TA; Mulatero, P
File in questo prodotto:
File Dimensione Formato  
Manuscript.docx

Accesso aperto

Tipo di file: PREPRINT (PRIMA BOZZA)
Dimensione 82.54 kB
Formato Microsoft Word XML
82.54 kB Microsoft Word XML Visualizza/Apri
Table 1. Features of FH-III families.docx

Accesso aperto

Tipo di file: PREPRINT (PRIMA BOZZA)
Dimensione 19.74 kB
Formato Microsoft Word XML
19.74 kB Microsoft Word XML Visualizza/Apri
Figure 1 - KCNJ5 germline mutations.tif

Accesso aperto

Tipo di file: PREPRINT (PRIMA BOZZA)
Dimensione 326.61 kB
Formato TIFF
326.61 kB TIFF Visualizza/Apri
Figure 2 - Index case's chromatogram-KCNJ5 G151R.tif

Accesso aperto

Dimensione 192.31 kB
Formato TIFF
192.31 kB TIFF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1676781
Citazioni
  • ???jsp.display-item.citation.pmc??? 10
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 31
social impact