One patient has mild brachydactyly but no endocrinopathy, whereas the other manifests brachydactyly, obesity, and target tissue resistance to thyrotropin and parathyroid hormone (PTH).
In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.
Heterozygous mice that inherited the disruption maternally (-m/+) exhibited PTH and TSH resistance, whereas those with paternal inheritance (+/-p) had normal hormone responsiveness.
We sought to identify the molecular defect in four unrelated patients who were thought to have PHP-Ia because of PTH and TSH resistance and mild AHO features.
PHP type Ib (PHP-Ib), usually defined by isolated renal resistance to PTH and sometimes mild TSH resistance, is due to a maternal loss of GNAS exon A/B methylation, leading to decreased Galphas expression in specific tissues.
This mutation was also found in the mother of this patient who was also noted to have short stature, obesity, brachydactyly and non progressive osteoma cutis, but no hormone resistance.We report a novel heterozygous mutation causing PHP1A with PTH and TSH resistance and AHO which has not been described previously.
In contrast, pseudohypoparathyroidism type Ib (PHP1B) is characterized mostly by resistance to PTH and often mild TSH resistance, usually without AHO features.
Finally, besides PTH deficiency, hypocalcemia can be due to PTH resistance in pseudohypoparathyroidism; when hormone resistance is generalized, patients can suffer from hypothyroidism due to TSH resistance.