A very rare disorder characterized by renal and/or
bony anomalies caused by their insensitivity to parathyroid hormone.
Pseudohypoparathyroidism (PHP) is a group of
diseases in which target cells (renal tubular or osseous) are insensitive to
Type I (PHP I) is caused by the inability of parathyroid hormone to activate
renal cell adenylcyclase.
Type Ia (Albright Hereditary Osteodystrophy) is the most frequent, is because of a
defect in the α subunit of the membrane-bound stimulatory G protein.
Type Ib (PHP IB) is probably caused by abnormalities at the parathyroid
Type II (PHP II) is because of the inability of cAMP to initiate the metabolic
events caused by stimulation of the parathyroid hormone receptor.
PHP type Ia and pseudopseudohypoparathyroidism
are caused by heterogenous mutations in the Gsα encoding exons of GNAS1
(chromosome 20q13.3); PHP type Ia occurs only if the mutation is inherited from a female
Pseudopseudohypoparathyroidism occurs if the mutation is inherited from a
male carrier. PHP type Ib has the same pattern of inheritance as is observed as for PHP
type Ia but the mutation has not been identified yet.
The skeletal and developmental features of type Ia
are those of the classic Albright hereditary osteodystrophy. Because the
stimulatory G protein involved in type Ia is required for responsiveness to
other hormones, hypothyroidism and gonadal dysfunction are common in this
type of PHP.
Hypocalcemia, hyperphosphatemia, and elevated
parathyroid hormone levels.
Children with PHP type Ia present with the
classic Albright hereditary osteodystrophy appearance: small stature with
moderate obesity, mild mental deficiency, rounded face with short neck,
dental aplasia or enamel dysplasia, and subcapsular cataracts. Radiography
shows osteoporosis, short metacarpal bones, and cone-shaped epiphyses.
Cervical vertebral anomalies may be present. Cutaneous or subcutaneous
calcifications. Hypocalcemia, which usually develops in the first years of
life, may lead to tetany, muscle cramps, or seizures. Children with PHP
types Ib and II have a normal physical appearance. PHP type I or II is
treated with vitamin D and oral phosphate binders. Spontaneous amelioration
of hypocalcemia may occur with time.
Check calcium and phosphate blood levels
and correct them as required; in a case of PHP type Ia, assess the presence
of other endocrinopathies (mainly hypothyroidism).
Hypocalcemia may lead to prolonged QT,
tetany, and laryngospasm. Hyperventilation should be avoided. In type Ia,
obesity may make venous access, mask ventilation, and laryngoscopy
Beware of hypocalcemia if there is
rapid administration of blood or fresh-frozen plasma.
Pseudopseudohypoparathyroidism: The patient has the
phenotype of Albright hereditary osteodystrophy but has normal calcium and
phosphate levels. It represents a variant of PHP type Ia.
Pseudohypohyperparathyroidism: Resistance to parathyroid
hormone is limited to the renal tubules; the bony response to elevated
parathyroid hormone levels is thus normal, leading to subperiosteal
resorption and ...