Pseudohypoparathyroidism
Encyclopedia
Pseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone
. 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
).
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".
is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but is biochemically normal.
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.
Parathyroid hormone
Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...
. Patients have a low serum calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
and high phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
, 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
Gs alpha subunit
The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...
).
Types
Types include:| Type | Description | OMIM | Gene |
|---|---|---|---|
| Type 1a | Has a characteristic phenotypic appearance (Albright's hereditary osteodystrophy Albright's hereditary osteodystrophy Albright’s hereditary osteodystrophy is form of osteodystrophy, otherwise known as Pseudohypoparathyroidism type 1a.-Characteristics:The disorder is characterized by a lack of responsiveness to parathyroid hormone, resulting in low serum calcium, high serum phosphate, and appropriately high serum... ), including short fourth and fifth metacarpals and a rounded facies Facies (medical) In medical contexts, facies are distinctive facial expressions associated with specific medical conditions.It comes from the Latin word for "face".As a fifth declension noun, "facies" can refer to the singular or plural.-Types:Examples include:... . It is most likely an autosomal dominant disorder. It is also associated with thyroid stimulating hormone resistance. |
GNAS1 GNAS1 GNAS complex locus, also known as GNAS, is a protein which in humans is encoded by the GNAS gene. The protein encoded by this gene is the stimulatory G-protein alpha subunit , a key component of many signal transduction pathways.- Gene :... |
|
| Type 1b | Lacks the physical appearance of type 1a, but is biochemically similar. It is associated with a methylation defect. | GNAS1 GNAS1 GNAS complex locus, also known as GNAS, is a protein which in humans is encoded by the GNAS gene. The protein encoded by this gene is the stimulatory G-protein alpha subunit , a key component of many signal transduction pathways.- Gene :... , STX16 STX16 Syntaxin-16 is a protein that in humans is encoded by the STX16 gene.It has been associated with pseudohypoparathyroidism type Ib.-Further reading:... |
|
| 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 Cyclic adenosine monophosphate Cyclic adenosine monophosphate is a second messenger important in many biological processes... response to PTH stimulation despite the inherent abnormality in calcium regulation. |
? |
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 pseudopseudohypoparathyroidismPseudopseudohypoparathyroidism
Pseudopseudohypoparathyroidism is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation...
is used to describe a condition where the individual has the phenotypic appearance of pseudohypoparathyroidism type 1a, but is biochemically normal.
Presentation and differential
Patients may present with features of hypocalcaemiaHypocalcaemia
In medicine, hypocalcaemia is the presence of low serum calcium levels in the blood, usually taken as less than 2.1 mmol/L or 9 mg/dl or an ionized calcium level of less than 1.1 mmol/L or 4.5 mg/dL. It is a type of electrolyte disturbance...
including carpo-pedal muscular spasms
Spasms
-Plot:Jason Kincaid has this massive serpent captured and brought to the US because it killed his brother and he now shares some kind of psychic link with it...
, cramping, tetany
Tetany
Tetany has two meanings, though both are related to the muscular system.* Tetany * Tetany The terms "tetany" and "tetanus" are distinct....
, 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
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
in the deep white matter
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
.
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
Dorsum
Dorsum is a Latin word. In science, it could mean:* Dorsum , the posterior side of an animal* Dorsum , a term used in astrogeology for a ridge* Theta Capricorni, a star on the back of the Goat...
of the hand is viewed in flexed
Flexion
In anatomy, flexion is a position that is made possible by the joint angle decreasing. The skeletal and muscular systems work together to move the joint into a "flexed" position. For example the elbow is flexed when the hand is brought closer to the shoulder...
position. This presentation is known as 'knuckle knuckle dimple dimple' sign. This is as opposed to Turner syndrome
Turner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
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
- hyperphosphatemiaHyperphosphatemiaHyperphosphatemia is an electrolyte disturbance in which there is an abnormally elevated level of phosphate in the blood. Often, calcium levels are lowered due to precipitation of phosphate with the calcium in tissues.-Signs and symptoms:...
- elevated parathyroid hormoneParathyroid hormoneParathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...
(hyperparathyroidismHyperparathyroidismHyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone . The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels...
)
See also
- HypoparathyroidismHypoparathyroidismHypoparathyroidism is decreased function of the parathyroid glands with under production of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany , and several other symptoms...
- PseudopseudohypoparathyroidismPseudopseudohypoparathyroidismPseudopseudohypoparathyroidism is an inherited disorder, named for its similarity to pseudohypoparathyroidism in presentation...
- HyperparathyroidismHyperparathyroidismHyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone . The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels...
- RicketsRicketsRickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
- Hypervitaminosis DHypervitaminosis DHypervitaminosis D is a state of vitamin D toxicity.The recommended daily allowance is 400 IU per day. Overdose has been observed at 1925 µg/d...