Non-Classical Presentations of Rare Hereditary Hypoparathyroidism: A Case Series of CASR, GNA11 and GATA3 Mutations.

BACKGROUND

Hereditary hypoparathyroidism (hypoPT) is a rare endocrine disorder caused by absent or insufficient parathyroid hormone (PTH) secretion. Genetic forms are uncommon and frequently underdiagnosed, particularly when clinical onset is atypical.

PURPOSE: We present a case series of three patients with genetic hypoPT caused by CASR, GNA11 and GATA3 mutations, highlighting atypical clinical presentation, diagnostic challenges and management approaches.

METHODS

Clinical data, biochemical results, and genetic findings were analysed in a case of three female patients with early-onset, nonsurgical hypoPT, focusing on presentation patterns, diagnostic pathways, and choice of treatment.

RESULTS

All patients exhibited chronic hypocalcemia, hyperphosphatemia, and low PTH without prior neck surgery, but had non-classical features leading to delayed diagnosis. Genetic testing identified pathogenic variants associated with autosomal dominant hypocalcemia types 1, 2, and Barakat syndrome. Age at symptom onset ranged from childhood to adolescence, whereas diagnosis was established only in late adolescence or adulthood. Major complications included intracranial calcifications (all cases), cataracts, and renal impairment. Initial presentations mimicked neurological, dermatological, and renal disorders, contributing to diagnostic delay. All patients required individualised therapy and multidisciplinary follow-up.

CONCLUSION

Genetic causes of hypoPT should be suspected in patients with early-onset or atypical presentations in the absence of neck surgery. This case series illustrates that timely genetic testing confirms the diagnosis and determines personalised therapy. Management requires careful titration of calcium, active vitamin D medication to avoid complications and may benefit from emerging treatments (long-acting PTH analogues). Early recognition and tailored interventions can improve patient outcomes and quality of life.