Pseudohypoparathyroidism

Pseudohypoparathyroidism
Classification and external resources
Specialty	Endocrinology
ICD-10	E20.1
ICD-9-CM	275.49
OMIM	103580 603233 203330
DiseasesDB	10835 10851
MedlinePlus	000364
eMedicine	med/1940
Patient UK	Pseudohypoparathyroidism
MeSH	D011547

Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Those with the condition have a low serum calcium and high phosphate, but the parathyroid hormone level (PTH) is actually appropriately high (due to the low level of calcium in the blood). Its pathogenesis has been linked to dysfunctional G Proteins (in particular, Gs alpha subunit). The condition is extremely rare, with an estimated overall prevalence of 7.2/1,000,000 or approximately 1/140000.

Types

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. It is also associated with thyroid stimulating hormone resistance.	103580	GNAS1
Type 1b	Lacks the physical appearance of type 1a, but is biochemically similar. It is associated with a methylation defect.	603233	GNAS1, STX16
Type 2	Also lacks the physical appearance of type 1a. 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".

Related conditions

The term pseudopseudohypoparathyroidism is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but is biochemically normal.

Condition		Appearance	PTH levels	Calcitriol	Calcium	Phosphates	Imprinting
Hypoparathyroidism		Normal	Low	Low	Low	High	Not applicable
Pseudohypoparathyroidism	Type 1A	Skeletal defects	High	Low	Low	High	Gene defect from mother (GNAS1)
	Type 1B	Normal	High	Low	Low	High	Gene defect from mother (GNAS1 and STX16)
	Type 2	Normal	High	Low	Low	High	?
Pseudopseudohypoparathyroidism		Skeletal defects	Normal	Normal	Normal	Normal	gene defect from father

Presentation and differential

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 closed fist position. This presentation is known as 'knuckle knuckle dimple dimple' sign (Archibald's 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.

Biochemical Findings

• hypocalcemia
• hyperphosphatemia
• elevated parathyroid hormone (hyperparathyroidism)
• Suppressed calcitriol levels

See also

• Hypoparathyroidism
• Pseudopseudohypoparathyroidism
• Hyperparathyroidism
• Rickets
• Hypervitaminosis D