Form Of Pseudohypoparathyroidism Research Articles

Acrodysostosis: A new form of pseudohypoparathyroidism?

Acrodysostosis: A new form of pseudohypoparathyroidism?

Pseudohypoparathyroidism Ia With Evans Syndrome

Pseudohypoparathyroidism Ia (Albright hereditary osteodystrophy or Albright syndrome) is a rare disease, caused by the resistance to the action of the parathyroid hormone in target tissues, such as the bone, kidney, and intestine, with consequent hypocalcemia and hyperphosphatemia and increased levels of parathyroid hormone. The phenotype of Albright syndrome includes 5 common features: brachydactyly, obesity, short stature, a round face, and mental retardation. We report on a child with a classic form of pseudohypoparathyroidism and associated Albright syndrome who developed Evans syndrome (ie, the cooccurrence of severe autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura). To our knowledge, no cases of Evans syndrome have been observed associated with pseudohypoparathyroidism 1a.

Autosomal‐Dominant Pseudohypoparathyroidism Type Ib is Caused by Different Microdeletions Within or Upstream of the GNAS Locus

The term pseudohypoparathyroidism (PHP) refers to the different disorders that are caused by mutations within GNAS or upstream of this complex genetic locus. GNAS gives rise to several different transcripts, including Gsalpha (alpha-subunit of heterotrimeric stimulatory G protein), XLalphas (extra-large variant of Gsalpha), and several additional sense and antisense transcripts. The complexity of the GNAS locus is furthermore reflected by a parent-specific methylation pattern of most of its different promotors. PHP can be divided into two major groups, PHP type Ia (PHP-Ia) and PHP type Ib (PHP-Ib). PHP-Ia is caused by heterozygous mutations affecting one of the 13 GNAS exons encoding Gsalpha or by large intragenic deletions. In contrast, PHP-Ib is caused by heterozygous deletions within STX16, the gene-encoding syntaxin 16, which is located more than 220 kb upstream of GNAS, or by deletions within GNAS involving exon NESP55 and two of the antisense exons. In either form of PHP, hormonal resistance develops only after maternal inheritance of the mutation, while paternal inheritance of the same molecular defect is not associated with endocrine abnormalities. In most familial cases of PHP-Ib, there is a loss of exon A/B methylation combined with active A/B transcription from both parental alleles, which leads to suppression of Gsalpha transcription in the proximal renal tubules and, therefore, PTH resistance.

Different Mutations Within or Upstream of the GNAS Locus Cause Distinct Forms of Pseudohypoparathyroidism

The term pseudohypoparathyroidism (PHP) refers to different disorders that are caused by mutations within GNAS or upstream of this complex genetic locus. GNAS gives rise to several different transcripts, including Gs alpha (alpha-subunit of the heterotrimeric stimulatory G protein), XL alpha s (extra-large variant of Gs alpha), and several additional sense and antisense transcripts. The complexity of the GNAS locus is furthermore reflected by a parent-specific methylation pattern of most of its different promoters. PHP can be divided into two major groups, PHP type Ia (PHP-Ia) and PHP type Ib (PHP-Ib). PHP-Ia is caused by heterozygous mutations affecting one of the 13 GNAS exons encoding Gs alpha. In contrast, PHP-Ib is caused by heterozygous deletions within STX16, the gene encoding syntaxin 16, which is located more than 220 kb upstream of GNAS, or by deletions within GNAS involving exon NESP55 and two of the antisense exons. In either form of PHP, hormonal resistance develops only after maternal inheritance of the mutation, while paternal inheritance of the same molecular defect is not associated with endocrine abnormalities. In most familial cases of PHP-Ib, there is a loss of exon A/B methylation combined with active A/B transcription from both parental alleles, which leads to suppression of Gs alpha transcription in the proximal renal tubules and, therefore, PTH resistance.

A new form of speudohypoparathyroidism type II with abnormal response to TRH: 37

A 12 years old Turkish girl, was admitted for tetany. She had laboratory findings of hypoparathyroidism (inorganic serum phosphorus : 7,5 mg/dl; calcium : 2,2 mEq/1; magnesium : 1,8 mg/dl). Blood alkaline phosphatase was strikingly increased as was iPTH. She has a normal phenotype but had moderate mental retardation. X-rays studies showed diffuse osteoporosis. The renal response to parathyroid extract administration was studied under several conditions : 1) there was a marked rise in urinary CAMP excretions but no increase in urinary phosphates. This type of response caracterizes pseudohypoparathyroidism (PHP) type II. 2) calcium therapy and vitamin D therapy did not modify this response. 3) the absence of restoration of normal renal responsiveness after an acute calcium infusion differentiates this case from the one described by Rodriguez. There was an excessive thyrotropin response to TRH injection whereas other studies of thyroid function were normal. With very low doses of vit. D (2000 U/day), serum calcium returned rapidly to normal values but phosphorus remained high and the renal unresponsiveness to PTH was unchanged. The TRH response also remained impaired. We propose that this could be a new form of pseudohypoparathyroidism (type III ?) whose calcemia can be controlled by low doses of vit. D.