Pseudohypoparathyroidism

[MIM 612 463]

Estimated prevalence of 0.3 to 1.1 /100,000. Heterogeneous group of diseases caused by insensitivity to parathyroid hormone, leading to renal and/or bone abnormalities.

From a genetic point of view, several types are identified:

type 1A [MIM 103,580] or Albright syndrome (see this term): autosomal dominant transmission of a loss of function mutation of the maternal allele of the GNAS gene (20q13.32); only the paternal allele is expressed. Resistance to parathyroid hormone is sometimes associated with resistance to TSH and gonadotropic hormones
type 1B [MIM 603 233]: resistance to parathyroid hormone at the renal level following the reduced expression of the maternal allele of the GNAS or STX16 gene at the renal level (mutation or epigenetic factor)
type 1C [MIM 612 462]: resistance to parathyroid hormones and other hormones; could be a variant of type 1A
type 2 [MIM 203 330]: isolated renal resistance to parathyroid hormone. The genetic origin is still unknown.

The GNAS gene encodes the stimulating alpha subunit (Gs), an intracellular G protein that stimulates the production of cAMP in response to certain physiological stimuli.

Clinical presentation:

In childhood, hypocalcemia can lead to crises of tetany, muscle cramps or seizures. Later: muscle weakness, bone pain.

Comparative table:

Name	phenotype	PTH rate	vit D	CA	phosphates	Erythrocyte gs
hypoparathyroidism	normal	low	low	low	high	normal
pseudo hypopara 1A	dysplasia	high	low	low	high	diminished
pseudo hypopara 1B	normal	high	low	low	high	normal
pseudo hypopara 1C	dysplasia	high	low	low	high	normal
pseudohypopara 2	normal	high	low	low	high	normal
pseudopseudo hypoparathyroidism	dysplasia	normal	normal	normal	normal	normal

Treatment: supplements of calcium and vitamin D and phosphate chelators by mouth.

Anesthetic implications:

check calcemia, avoid hyperventilation. Make sure that there are no other associated endocrine abnormalities (types Ia and Ic)

References :

- Kahloul N, Chaari W, Boughamoura L, Charfeddine L, Khammeri S, Amri F.
Un syndrome de Fahr révélateur d’une pseudohypoparathyroïdie.
Arch Pédiatr 2009 ; 16 :444-8.

Updated: May 2022