Primary hyperparathyroidism in children and adolescents.

Area of Science:

• Pediatric Endocrinology
• Human Genetics
• Molecular Endocrinology

Background:

• Primary hyperparathyroidism (PHPT) is common in adults but causes greater morbidity in children and adolescents.
• Pediatric PHPT frequently presents with symptomatic hypercalcemia, kidney stones, abdominal pain, and skeletal fragility.
• Germline inactivating mutations in the calcium-sensing receptor (CASR) gene are notably prevalent in young PHPT patients.

Purpose of the Study:

• To highlight the distinct clinical features and genetic underpinnings of PHPT in pediatric populations.
• To differentiate between severe forms of PHPT caused by biallelic CASR mutations and milder forms associated with heterozygous mutations.
• To emphasize the importance of accurate diagnosis for appropriate management of PHPT in children and adolescents.

Main Methods:

• Review of clinical presentations and genetic findings in pediatric PHPT cases.
• Analysis of the correlation between CASR gene mutation types (biallelic vs. heterozygous) and disease severity.
• Comparison of management strategies based on distinct PHPT phenotypes.

Main Results:

• Biallelic CASR mutations lead to neonatal severe hyperparathyroidism, a critical condition.
• Heterozygous CASR mutations are typically associated with familial hypocalciuric hypercalcemia, a generally benign condition.
• Distinguishing between these genetic forms is essential for determining the need for parathyroidectomy.

Conclusions:

• PHPT in children requires careful evaluation due to potential for significant morbidity.
• CASR gene mutation analysis is critical for classifying pediatric PHPT and informing treatment.
• Management strategies should be tailored to the specific genetic cause and clinical presentation of PHPT in young patients.