Normocalcaemic pseudohypoparathyroidism with unusual phenotype

Area of Science:

• Pediatric Endocrinology
• Skeletal Dysplasias
• Hormone Resistance Syndromes

Background:

• Pseudohypoparathyroidism (PHP) is a group of genetic disorders characterized by resistance to parathyroid hormone (PTH).
• PHP typically presents with hypocalcemia, hyperphosphatemia, and characteristic physical features (Albright's hereditary osteodystrophy).
• This case explores a variant presentation of PHP with distinct biochemical and clinical findings.

Observation:

• A 4-year-old boy presented with radiological hyperparathyroidism, osteosclerosis, and femoral head necrosis.
• Despite normal plasma biochemistry, he exhibited elevated parathyroid hormone (PTH) levels and subnormal cyclic AMP responses to PTH.
• The patient had deafness and unusual facies but did not display the classic Albright's hereditary osteodystrophy phenotype.

Findings:

• Vitamin D therapy induced sustained hypercalcemia and decreased plasma phosphorus levels.
• Surgical removal of hyperplastic parathyroid glands resulted in hypocalcemia and a rise in plasma phosphorus.
• Post-operatively, the patient remained unresponsive to exogenous PTH, indicating persistent hormone resistance.

Implications:

• This case suggests a form of pseudohypoparathyroidism (PHP) distinct from Albright's hereditary osteodystrophy.
• The findings highlight the heterogeneity of PHP phenotypes and PTH resistance.
• The patient demonstrated some residual skeletal and renal responsiveness to PTH, suggesting partial hormone signaling.