Pseudohypoparathyroidism is a rare disease that was discovered
initially by Fuller Albright and his colleagues in 1942 when they found group a
of patients who presented with pictures of hypoparathyroidism (hypocalcemia,
hyperphosphatemia) but their calcium and phosphate level failed to show
responses after repeated injections of bovine parathyroid extract. It was
concluded that the mechanism was end organ resistance that primarily impairs
the renal actions of PTH, rather than deficiency in the hormones. PHP was
divided into type 1 and type 2, and type 1 subdivided to 1a, 1b, 1c, with the
most common form being type 1a. Presence of some distinctive features (short
stature, rounded face, obesity, cutaneous ossification and metacarpophalangeal
abnormalities) along with parathyroid hormone resistance indicate that which is
known as Albright’s Hereditary Osteodystrophy.
PHP-1a is caused by heterozygous loss-of-function mutations in
the Gs-alpha isoform of the GNAS gene on the maternal allele, which results in
expression of the protein only from the paternal allele. Pseudopseudo
hypoparathyroidism (PPHP) is a similar disorder characterized by features of
AHO but with normal biochemistry and is caused by “mutations resulting in loss
of function of the Gs-alpha isoform of the GNAS gene on the paternal allele and
resultant expression of the protein only from the maternal allele”. Patients
with type 1b have Renal PTH resistant hypocalcaemia and hyperphosphatemia, and
imprinting/methylation defects at the GNAS locus, but they lack the features of
AHO.
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