Autosomal Dominant Hypocalcemia Type 1: A Systematic Review

Area of Science:

• Endocrinology
• Genetics
• Nephrology

Background:

• Autosomal dominant hypocalcemia type 1 (ADH1) is a rare hypoparathyroidism subtype resulting from activating calcium-sensing receptor (CASR) gene variants.
• These variants disrupt calcium homeostasis, leading to hypocalcemia and hypercalciuria, often managed with calcium and activated vitamin D.
• Conventional therapy can exacerbate hypercalciuria, increasing the risk of renal complications.

Approach:

• A systematic literature review was performed, analyzing published reports from 1994 to 2021.
• The review cataloged CASR variants, defined the ADH1 clinical spectrum, and assessed treatment effects.
• Data from 191 patients and 113 unique CASR variants were analyzed.

Key Points:

• ADH1 presents with a spectrum of severity, with 41% of patients experiencing severe symptoms like seizures.
• Diagnosis reveals hypocalcemia (99%), hyperphosphatemia (59%), low PTH (57%), and hypercalciuria (34%).
• Conventional therapy increased hypercalciuria by 91% and was associated with a 75% incidence of renal complications, including nephrocalcinosis and nephrolithiasis.

Conclusions:

• ADH1 is frequently severe at presentation and carries a significant risk of renal complications.
• Hypercalciuria is a key factor linking ADH1 to renal complications.
• The findings underscore the limitations of conventional therapy and suggest a need for novel treatment strategies for ADH1.