Disease relevance of Pseudohypoparathyroidism

• In hypoparathyroidism and pseudohypoparathyroidism, pharmacologic doses of vitamin D correct hypocalcemia, but the mechanism is unknown [1].
• Maternally derived mutations are usually associated with resistance to parathyroid hormone termed "pseudohypoparathyroidism type Ia." Paternally derived mutations are associated with AHO but usually normal hormone responsiveness, known as "pseudo-pseudohypoparathyroidism." These observations can be explained by tissue-specific GNAS1 imprinting [2].
• This finding supports the concept that PTH-mediated bone resorption may contribute to the maintenance of serum Ca in normocalcemic pseudohypoparathyroidism [3].
• Serum PTH and calcium were measured in five normal subjects, two patients with pseudohypoparathyroidism, and fourteen patients with primary hyperparathyroidism, twelve of whom were subsequently found to have parathyroid adenomas [4].
• In five of these patients, a differential diagnosis was made (Ohdo-like blepharophimosis syndrome, Alstrøm syndrome, Cohen syndrome, Bardet-Biedl syndrome, and pseudohypoparathyroidism) [5].

Psychiatry related information on Pseudohypoparathyroidism

• Mental deficiency in pseudohypoparathyroidism type I is associated with Ns-protein deficiency [6].
• In six patients with pseudohypoparathyroidism (PHP) who were deficient in guanine nucleotide-binding stimulatory protein (Ns) activity, the response to endogenous arginine vasopressin (AVP) was tested during water deprivation [7].

High impact information on Pseudohypoparathyroidism

• Epigenetic defects in the imprinted GNAS cluster are associated with pseudohypoparathyroidism type Ib [8].
• If activity of the N protein is reduced in other tissues, this deficiency could cause the resistance of target organs in pseudohypoparathyroidism to parathyroid hormone and other hormones that work via cyclic AMP [9].
• Prolactin deficiency in pseudohypoparathyroidism [10].
• These data suggest that 1,25-dihydroxycholecalciferol deficiency may explain the skeletal resistance, but not the renal resistance, often present in classic pseudohypoparathyroidism [11].
• To evaluate the role of serum calcium in human insulin secretion, insulin responses after a 100-g oral glucose load were studied in nine patients with primary hyperparathyroidism, five with idiopathic hypoparathyroidism, three with pseudohypoparathyroidism and one with normocalcemic secondary hyperparathyroidism [12].

Chemical compound and disease context of Pseudohypoparathyroidism

• These findings suggest an impaired conversion of 25-hydroxyvitamin D to 1 alpha,25-dihydroxyvitamin D in both hypoparathyroidism and pseudohypoparathyroidism [1].
• Altered activity of the nucleotide regulatory site in the parathyroid hormone-sensitive adenylate cyclase from the renal cortex of a patient with pseudohypoparathyroidism [13].
• In nine patients with pseudohypoparathyroidism during the treatment with active vitamin D3, serum osteocalcin and plasma 1,25(OH)2D were normal (6.8 +/- 1.47 ng/ml and 27.2 +/- 6.0 pg/ml, respectively) [14].
• Pseudohypoparathyroidism includes a genotypically diverse group of syndromes of primary resistance to hormones whose actions are mediated by cyclic adenosine 3':5'-monophosphate [15].
• Resistance to multiple hormones in patients with pseudohypoparathyroidism. Association with deficient activity of guanine nucleotide regulatory protein [16].

Biological context of Pseudohypoparathyroidism

• In patients with isolated renal resistance to PTH (pseudohypoparathyroidism type IB), the exon 1A promoter region has a paternal-specific imprinting pattern on both alleles (unmethylated, transcriptionally active), suggesting that this region is critical for the tissue-specific imprinting of G(s)alpha [17].
• Heterozygous inactivating mutations in the GNAS1 exons (20q13.3) that encode the alpha-subunit of the stimulatory G protein (Gsalpha) are found in patients with pseudohypoparathyroidism type Ia (PHP-Ia) and in patients with pseudo-pseudohypoparathyroidism (pPHP) [18].
• Paternal uniparental isodisomy of chromosome 20q--and the resulting changes in GNAS1 methylation--as a plausible cause of pseudohypoparathyroidism [18].
• Although the molecular basis of pseudohypoparathyroidism type 1b (PHP type 1b) remains unknown, a defect in imprinting at the GNAS1 locus has been suggested by the consistent finding of paternal-specific patterns of DNA methylation on maternally inherited GNAS1 alleles [19].
• Relationship of estrogen and pregnancy to calcium homeostasis in pseudohypoparathyroidism [3].

Anatomical context of Pseudohypoparathyroidism

• A series of clinical studies suggest that the primary defect underlying pseudohypoparathyroidism is an abnormality of the parathyroid hormone-receptor-adenylate cyclase complex of the renal cortical cell plasma membrane [13].
• Erythrocytes of patients with pseudohypoparathyroidism exhibit decreased activity of a membrane protein that is required for functional coupling of hormone receptors and catalytic adenylate cyclase [20].
• Selective resistance to parathyroid hormone in cultured skin fibroblasts from patients with pseudohypoparathyroidism type Ib [21].
• The stimulatory G protein alpha-subunit Gs alpha is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B [22].
• To assess whether placentas from women with disorders of vitamin D metabolism could also produce 1,25-(OH)2D3, we measured the placental production rates of 1,25-(OH)2D3 in three women with PTH-resistant hypoparathyroidism (pseudohypoparathyroidism) during four separate pregnancies [23].

Gene context of Pseudohypoparathyroidism

• A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS [24].
• Distinct patterns of abnormal GNAS imprinting in familial and sporadic pseudohypoparathyroidism type IB [25].
• Normal parathyroid hormone responsiveness of bone-derived cells from a patient with pseudohypoparathyroidism [26].
• Serum FGF-23 regulation was studied in patients with hypoparathyroidism or pseudohypoparathyroidism treated with calcitriol [27].
• Pseudohypoparathyroidism type Ib (PHP-Ib) is thought to be caused by a PTH/PTH-related peptide (PTHrP) receptor defect [28].

Analytical, diagnostic and therapeutic context of Pseudohypoparathyroidism

• The intravenous infusion of edetate disodium (disodium EDTA) showed a normal phosphaturic and cyclic adenosine monophosphate response, ruling out the diagnosis of pseudohypoparathyroidism [29].
• We prospectively investigated eight patients, aged 13 to 31 years, with long-standing hypocalcemia due to idiopathic hypoparathyroidism or pseudohypoparathyroidism by echocardiography [30].
• Changes in plasma adenosine 3'5' (cAMP) and guanosine (cGMP) monophosphate, measured by specific radioimmunoassay, after 150 USP/M2 of bovine parathyroid hormone (bPTH) iv administered were studied in children with pseudohypoparathyroidism, and idiopathic hypoparathyroidism, and in normal controls [31].
• Sensorineural hearing loss owing to deficient G proteins in patients with pseudohypoparathyroidism: results of a multicentre study [32].
• Immunohistochemistry revealed intense staining of calbindin-D28K and parvalbumin at sites of calcium deposits both in the present case and in a case of pseudohypoparathyroidism, whereas these proteins were not localized to calcium deposits in the cerebellum of a Fahr's disease brain [33].

References