| Pseudohypoparathyroidism | |
|---|---|
| Classification and external resources | |
| ICD-10 | E20.1 |
| ICD-9 | 275.49 |
| DiseasesDB | 10835 10851 |
| MedlinePlus | 000364 |
| eMedicine | med/1940 |
| MeSH | D011547 |
Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone.[1] Patients have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is actually appropriately high (due to the hypocalcemia). Its pathogenesis has been linked to dysfunctional G Proteins (in particular, Gs alpha subunit).
Contents |
Types include:
| Type | Description | OMIM | Gene |
|---|---|---|---|
| Type 1a | 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.[2] It is also associated with thyroid stimulating hormone resistance.[3] | 103580 | GNAS1 |
| Type 1b | Lacks the physical appearance of type 1a, but is biochemically similar.[4] It is associated with a methylation defect.[5][6] | 603233 | GNAS1, STX16 |
| Type 2 | Also lacks the physical appearance of type 1a.[7] 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. | 203330 | ? |
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".[8]
The term pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but is biochemically normal.
Patients may present with features of hypocalcaemia including carpo-pedal muscular spasms, cramping, tetany, and if the calcium deficit is severe, generalized seizures. IQ is typically mildly depressed or unaffected. Additional characteristics include short stature, obesity, developmental delay, and calcification of the basal ganglia in the deep white matter of the brain.
Type 1a Pseudohypoparathyroidism is clinically manifest by bone resorption with blunting of the fourth and fifth knuckles of the hand, most notable when the dorsum of the hand is viewed in flexed position. This presentation is known as 'knuckle knuckle dimple dimple' sign. This is as opposed to Turner syndrome which is characterized by blunting of only the fourth knuckle, and Down's syndrome, which is associated with a hypoplastic middle phalanx.
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