Inherited condition caused by a lack of parathyroid
hormone resulting in hypocalcemia and hyperphosphatemia and their clinical
Endocrine disorder of the parathyroid gland as a
consequence of primary or secondary lack of parathormone secretion. Primary
forms result from many rare diseases.
Primary hypoparathyroidism is rare; fewer than 1000
cases of the idiopathic form, familial or not, have been reported. Rare in
Both autosomal dominant (gene map locus 3q13) and X-linked (also related
to a mutation in the parathyroid hormone gene) forms of familial idiopathic
hypoparathyroidism have been reported.
- X-Linked Agenesis of Parathyroid Gland: Gene map locus is Xq26-q27.
- Hypoparathyroidism-Retardation-Dysmorphism Syndrome (HRDS): Autosomal recessive.
- Sanjad-Sakati Syndrome (Congenital Hypoparathyroidism with Growth Retardation, Developmental
Delay, and Dysmorphism): Gene map location is 1q42-43.
Primary and secondary hypoparathyroidism are
conditions in which there is a deficiency of parathyroid hormone. This
deficiency induces hypocalcemia and decreases calcium resorption from bone
and calcium absorption from gastrointestinal tract by preventing synthesis
of vitamin D. The lack of parathyroid hormone stops the osteolytic effect of
vitamin D and results in a decrease in bone metabolism. The decreased
calcium concentration in the motor plate induces neuromuscular
hyperexcitability. A very sensitive extracellular calcium-sensing receptor,
coupled to a G protein, has been isolated from parathyroid, kidney, and
brain cells. Some autosomal dominant forms of hypocalcemia result from
activating mutations of this extracellular calcium-sensing receptor, which
inhibits parathyroid hormone exocytosis (mechanism is unknown).
In primary hyperparathyroidism, note hypocalcemia,
hypomagnesemia, hyperphosphoremia, and low serum level of parathyroid
hormone. Urinary excretion of calcium, phosphorus, and cAMP is decreased.
Ellsworth Howard test (infusion of 200 IU of parathyroid hormone) induces an
increase of cAMP and phosphaturia. Intracerebral calcifications on CT scan.
In neonates, the symptoms of hyperparathyroidism are
respiratory distress, cyanosis, apnea, hypertonia, agitation, and tetany.
In infants, the symptoms are seizures and tinnitus crisis with inspiratory stridor,
laryngospasm, and unexplained tachycardia. In children, tinnitus is the most frequent
sign, with seizures that can be typical or not. Hypocalcemia may be
life-threatening and can cause nephrocalcinosis and renal lithiasis.
Primary forms are related to many rare diseases, mostly genetically inherited.
Autoimmune diseases: Type I autoimmune polyglandular syndrome (or HAM syndrome) results in
primary hypoparathyroidism by 10 years of age as a result of destruction of the
parathyroids. Other types of autoimmune hypoparathyroidism may exist alone,
in sporadic or familial forms.
Congenital diseases and syndromeswith agenesis or hypoplasia of the parathyroid glands include the following:
Isolated primary hypoparathyroidism
X-linked primary hypoparathyroidism (band Xq26-Xq27)
X autosomal recessive primary hypoparathyroidism
Branchial dysgenesis (DiGeorge syndrome)
Chromosomal defects dup(1q), del(5p), dup(8q), del(10q), del(22q)
Isolated autosomal dominant conditions
Isolated autosomal recessive conditions