Pseduohypoparathyroidism vs Pseudopseudohypoparathyroidsm
Understanding this distinction is important for proper diagnosis, as it helps differentiate between these two genetically related conditions with similar physical manifestations but differing biochemical profiles.
Pseudopseudohypoparathyroidism
- PPHP is caused by heterozygous mutations in the GNAS gene, the same gene responsible for PHP, but only in the paternal allele.
- Maternal allele of the GNAS gene is normal, so the gene function is not impaired in the tissues where the mutation is expressed (such as kidneys, bones, and adipose tissue).
- This results in the physical features of PHP (e.g., short stature, round face, and obesity) but without the biochemical abnormalities associated with PHP).
Key Features of PPHP:
- Physical Features:
- Individuals with PPHP often have the same physical features as those with PHP (e.g., short stature, obesity, round face, and sometimes subcutaneous calcifications).
- These features are due to the imprinting of the GNAS gene, which results in Albright’s hereditary osteodystrophy.
- Biochemical Features:
- In contrast to PHP, individuals with PPHP do not have PTH resistance. They do not experience the same hypocalcemia or elevated PTH associated with PHP.
- Urinary cAMP levels in response to PTH are normal in PPHP, because there is no resistance to the effects of PTH. This is one of the major distinguishing features between PHP and PPHP.
Pseudohypoparathyroidism (PHP) vs Pseudopseudohypoparathyroidism (PPHP):
| Feature | Pseudohypoparathyroidism (PHP) | Pseudopseudohypoparathyroidism (PPHP) |
| Cause | Maternal inheritance of a mutation in the GNAS gene. | Paternal inheritance of a mutation in the GNAS gene. |
| Physical features | Albright’s hereditary osteodystrophy (short stature, obesity, round face, subcutaneous calcifications). | Same physical features (short stature, obesity, round face) as PHP. |
| PTH levels | Elevated PTH (due to PTH resistance in the kidneys and other tissues). | Normal PTH levels because tissues respond normally to PTH. |
| Urinary cAMP response to PTH | Low or absent urinary cAMP despite elevated PTH levels (due to PTH resistance). | Normal urinary cAMP response to PTH (because there is no PTH resistance). |
| Calcium levels | Hypocalcemia (low calcium) due to PTH resistance. | Normal calcium levels (since there is no PTH resistance). |
Key Diagnostic Difference:
- PPHP presents with the physical features of pseudohypoparathyroidism, but urinary cAMP levels will be normal in response to PTH, differentiating it from pseudohypoparathyroidism where urinary cAMP is low despite high PTH.
Take home points
- Pseudohypoparathyroidism (PHP) is characterized by PTH resistance and low urinary cAMP despite high PTH levels.
- Pseudopseudohypoparathyroidism (PPHP) shares the physical features of PHP (due to imprinting of the GNAS gene) but does not have PTH resistance, and urinary cAMP levels remain normal in response to PTH.