From the Research
Pseudohypoparathyroidism type 1b (PHP1b) is characterized by resistance to parathyroid hormone (PTH) primarily in the kidneys, without the physical features of Albright hereditary osteodystrophy, and is typically associated with hypocalcemia, hyperphosphatemia, and elevated PTH levels, as reported in a recent case study 1.
Clinical Features
The clinical presentation of PHP1b includes symptoms such as paresthesias, muscle cramps, tetany, and seizures due to hypocalcemia. Patients with PHP1b typically have a normal physical appearance without short stature, round face, or brachydactyly, as noted in a study published in the Journal of pediatric endocrinology & metabolism 2.
- Hypocalcemia
- Hyperphosphatemia
- Elevated PTH levels
- Normal vitamin D status
- Paresthesias
- Muscle cramps
- Tetany
- Seizures
Biochemical Features
Biochemically, PHP1b shows resistance to PTH with impaired urinary cAMP and phosphate excretion in response to PTH administration.
- Low serum calcium (typically 6.5-8.0 mg/dL)
- Elevated phosphate (>5.0 mg/dL)
- Markedly increased PTH levels (often 2-10 times normal)
- Impaired urinary cAMP and phosphate excretion in response to PTH administration
Imaging Features
Imaging may reveal basal ganglia calcifications on brain CT, particularly in patients with longstanding hypocalcemia.
- Basal ganglia calcifications on brain CT
- Normal bone radiographs without evidence of rickets or osteomalacia
Molecular Features
PHP1b results from epigenetic alterations in the GNAS locus, specifically loss of methylation at the maternal GNAS A/B differentially methylated region, leading to decreased Gsα protein expression in renal proximal tubules, as demonstrated in a study published in the Journal of bone and mineral research 3.
- Loss of methylation at the maternal GNAS A/B differentially methylated region
- Decreased Gsα protein expression in renal proximal tubules
Treatment
Treatment focuses on correcting hypocalcemia with calcium supplements (1-3 g elemental calcium daily) and active vitamin D analogs (calcitriol 0.25-2.0 μg daily), with dose adjustments based on serum calcium, phosphate, and PTH levels, as recommended in a recent study 1.
- Calcium supplements (1-3 g elemental calcium daily)
- Active vitamin D analogs (calcitriol 0.25-2.0 μg daily)
- Dose adjustments based on serum calcium, phosphate, and PTH levels