Etiology

Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone.[1] Those with the condition have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is appropriately high (due to the low level of calcium in the blood).

Types include:

Type 1a (OMIM 103580): Has a characteristic phenotypic appearance (Albright's hereditary osteodystrophy), including short fourth and fifth metacarpals and a rounded facies. It is most likely an autosomal dominant disorder.[3] It is also associated with thyroid stimulating hormone resistance. Caused by GNAS1 mutation.[4]
Type 1b (OMIM 603233): Lacks the physical appearance of type 1a, but is biochemically similar.[5] It is associated with a methylation defect in the A/B exon of GNAS1, caused by STX16 disruption.[6][7]
Type 2 (OMIM 203330): Also lacks the physical appearance of type 1a.[8] Since the genetic defect in type 2 is further down the signalling pathway than in type 1, there is a normal cAMP response to PTH stimulation despite the inherent abnormality in calcium regulation. The specific gene is not identified.

While biochemically similar, type 1 and 2 disease may be distinguished by the differing urinary excretion of cyclic AMP in response to exogenous PTH.

Some sources also refer to a "type 1c" (OMIM 612462).[9] The phenotype is the same as in type 1a, but red blood cells show normal Gs activity. As it is also caused by a GNAS mutation, it is not clear whether it should be considered an entity separate from Ia.[10]

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Etiology

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