Clinical and laboratory investigation revealed markedly elevated PTH, low ionized calcium, elevated phosphorus, TSH resistance, and skeletal evidence of hyperparathyroidism, leading to the diagnosis of PHP1B.
In contrast, pseudohypoparathyroidism type Ib (PHP1B) is characterized mostly by resistance to PTH and often mild TSH resistance, usually without AHO features.
Pseudohypoparathyroidism type Ib (PHP1B) is characterized primarily by resistance to parathyroid hormone (PTH) and thus hypocalcemia and hyperphosphatemia, in most cases without evidence for Albright hereditary osteodystrophy (AHO).
Proximal tubular resistance to parathyroid hormone (PTH) resulting in hypocalcemia and hyperphosphatemia are preeminent abnormalities in pseudohypoparathyroidism type Ib (PHP1B), but resistance toward other hormones as well as variable features of Albright's Hereditary Osteodystrophy (AHO) can occur also.
However, there is no PTH resistance in the distal renal tubules nor in bone cells; consequently, patients with PHP1B have reduced urinary calcium excretion and can readily mobilise calcium (and phosphate) from the skeleton.
Pseudohypoparathyroidism type Ib (PHP1B) is caused by proximal tubular resistance to parathyroid hormone that occurs in most cases in the absence of Albright's Hereditary Osteodystrophy (AHO).
Depending on the assay used for evaluating these patients, plasma PTH levels were either low or profoundly elevated, thus leading to ambiguities regarding the underlying diagnosis, namely IHP or PHP1B.
Hypocalcemia and hyperphosphatemia because of resistance toward parathyroid hormone (PTH) in the proximal renal tubules are the most prominent abnormalities in patients affected by pseudohypoparathyroidism type Ib (PHP-Ib).
Pseudohypoparathyroidism type 1b (PHP-Ib) is characterized by renal resistance to PTH (and, sometimes, a mild resistance to TSH) and absence of any features of Albright's hereditary osteodystrophy.
Pseudohypoparathyroidism (PHP) is associated with compromised signal transductions via PTH receptor (PTH-R) and other G-protein-coupled receptors including GHRH-R. To date, while GH deficiency (GHD) has been reported in multiple patients with PHP-Ia caused by mutations on the maternally expressed GNAS coding regions and in two patients with sporadic form of PHP-Ib accompanied by broad methylation defects of maternally derived GNAS differentially methylated regions (DMRs), it has not been identified in a patient with an autosomal dominant form of PHP-Ib (AD-PHP-Ib) accompanied by an STX16 microdeletion and an isolated loss of methylation (LOM) at exon A/B-DMR.
Pseudohypoparathyroidism type Ib (PHP-Ib) is a rare imprinting disorder characterized by end-organ resistance to PTH and, frequently, to thyroid-stimulating hormone.
Pseudohypoparathyroidism type 1B (PHP1B) patients have PTH resistance at the renal proximal tubule and develop hypocalcemia and secondary hyperparathyroidism.
Maternally inherited 3-kb STX16 deletions cause autosomal dominant pseudohypoparathyroidism type Ib (PHP-Ib) characterized by PTH resistance with loss of methylation restricted to the GNAS exon A/B.
PHP-Ib patients have isolated Parathormone (PTH) resistance and GNAS epigenetic defects while PHP-Ia cases present with hormone resistance and characteristic features jointly termed as Albright's Hereditary Osteodystrophy (AHO) due to maternally inherited GNAS mutations or similar epigenetic defects as found for PHP-Ib.
Our findings suggest that PTH in this PHP-Ib genotype can increase cortical thickness due to its anabolic effect on endocortical bone, and underscore the heterogeneity in the skeletal phenotype among patients with PHP-Ib.
Most patients with pseudohypoparathyroidism type Ib (PHP-Ib) exhibit imprinting defects affecting the maternal GNAS allele, which are thought to reduce/abolish Gsalpha expression in renal proximal tubules and thereby cause resistance to PTH.
Pseudohypoparathyroidism type Ib (PHPIb) is characterized by parathyroid hormone (PTH) resistance, which can lead to hypocalcemia, hyperphosphatemia, and increased serum PTH.
Pseudohypoparathyroidism type Ib (PHP-Ib) is characterized by hypocalcemia and hyperphosphatemia due to proximal renal tubular resistance to PTH but without evidence for Albright's hereditary osteodystrophy.
However, subsequent testing showed hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone levels consistent with pseudohypoparathyroidism type Ib.
Phenotypic and molecular genetic aspects of pseudohypoparathyroidism type Ib in a Greek kindred: evidence for enhanced uric acid excretion due to parathyroid hormone resistance.
However, methylation-status analysis revealed a bialleic methylation defect in GNAS exon 1A, indicating that a GNAS-imprinting defect is the cause of her PTH resistance, as commonly observed in pseudohypoparathyroidism type IB.
Patients with pseudohypoparathyroidism type Ib (PHP-Ib) have hypocalcemia and hyperphosphatemia due to renal parathyroid hormone (PTH) resistance, but lack physical features of Albright hereditary osteodystrophy.
Patients with PTH resistance in the absence of Albright hereditary osteodystrophy (PHP1B) have an imprinting defect of the G(s)alpha gene resulting in both alleles having a paternal epigenotype, which would lead to a more moderate level of thyroid-specific G(s)alpha deficiency.