Familial hyperaldosteronism type III.

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Primary aldosteronism is a leading cause of endocrine hypertension, with familial forms (FH-I to FH-IV) identified.
• FH-III is specifically linked to germline mutations in the KCNJ5 gene, which encodes the Kir3.4 potassium channel.

Observation:

• KCNJ5 mutations disrupt the channel's selectivity filter, causing aberrant ion currents, reduced potassium selectivity, and increased sodium influx.
• This ion imbalance elevates intracellular calcium, driving excessive aldosterone biosynthesis.

Findings:

• Six distinct KCNJ5 mutations have been identified in eleven families with FH-III.
• Patients typically present with severe, early-onset hyperaldosteronism, hypokalemia, and symptoms resembling diabetes insipidus.
• Resistance to pharmacological treatments is common, often necessitating bilateral adrenalectomy.

Implications:

• Understanding the genetic basis of FH-III is crucial for accurate diagnosis and management.
• The review covers genetics, pathology, diagnostics, clinical presentation, and therapeutic strategies for FH-III.
• A new case of FH-III in an Italian patient with a Gly151Arg mutation is presented, expanding the known mutational spectrum.