Sorted By Test Name - Mayo Medical Laboratories

oversensing of Ca(++), resulting in suppression of PTH secretion and consequently hypoparathyroidism.
All activating mutations described are functionally dominant and disease inheritance is therefore
autosomal dominant. However, sporadic cases also occur. Autosomal dominant hypoparathyroidism may
account for many cases of idiopathic hypoparathyroidism. Disease severity depends on the degree of gain
of function, spanning the spectrum from mild hypoparathyroidism, which is diagnosed incidentally, to
severe and early onset disease. In addition, while the majority of patients suffer only from
hypoparathyroidism, a small subgroup with extreme gain of function mutations suffer from concomitant
inhibition of renal sodium-chloride transport. These individuals may present with additional symptoms of
hypokalemic metabolic alkalosis, hyperreninemia, hyperaldosteronism, and hypomagnesemia, consistent
with type V Bartterâ€s syndrome.
Useful For: Confirming or ruling out a suspected diagnosis of familial hypocalciuric hypercalcemia As
part of the workup of some patients with parathyroid hormone Confirming or ruling out a suspected
diagnosis of neonatal severe primary hyperparathyroidism Confirming or ruling out a suspected diagnosis
of autosomal dominant hypoparathyroidism As part of the workup of idiopathic hypoparathyroidism As
part of the workup of patients with Bartter's syndrome
Interpretation: Patients with apparent mild-to-moderate hyperparathyroidism, who have a ratio of
calcium clearance to creatinine clearance that is 0.01. These patients can be difficult or impossible to
distinguish from individuals with primary hyperparathyroidism (PTH). A diagnosis of FHH should
therefore be considered in all PHT patients who do not have markedly elevated serum calcium, low
phosphate, high urinary calcium excretion, and demonstrable parathyroid tumor, indicative of typical
PHT. CASR mutation screening, as described above, can assist in reaching a definite diagnosis. Severe
hypercalcemia and hyperparathyroidism in neonates and small infants is highly suspicious of neonatal
severe primary hyperparathyroidism (NSPHT), but can be caused by other diseases. While treatment must
not be delayed until a final diagnosis is reached, CASR mutation screening allows confirmation or
exclusion of NSPHT. Identification of homozygous or compound heterozygous inactivating CASR
mutations or a known dominant negative CASR mutation confirms the diagnosis, while identification of
novel alterations(s) increases the likelihood of a NSPHT diagnosis, but does not confirm it until family
studies or functional studies support its pathogenicity. Absence of any mutations or the presence of
polymorphism(s) that are known to be functionally neutral makes the diagnosis very unlikely (see
Cautions for exceptions). Children with isolated hypoparathyroidism and no other syndrome-related
abnormalities are likely to suffer from autosomal dominant hypoparathyroidism (ADH). Identification of
a heterozygous activating CASR mutation confirms this diagnosis, while identification of novel
alteration(s) increases the likelihood of an ADH diagnosis, but does not confirm it until family studies or
functional studies support its pathogenicity. Absence of any mutations or the presence of
polymorphism(s) that are known to be functionally neutral makes the diagnosis unlikely (see Cautions for
exceptions). Since ADH cases may have mild disease that does not present in childhood, all cases of
apparent idiopathic hypoparathyroidism should be considered for CASR mutation screening. The correct
diagnosis is important, as ADH patients are more susceptible to the side effects of 1,25-dihydroxy vitamin
D therapy than other patients with hypoparathyroidism and because of genetic counseling considerations.
CASR mutation screening, as described above, can assist in reaching a definite diagnosis. Patients with
Bartter's syndrome who have hypocalcemia and inappropriately low serum PTH levels that do not change
after repletion of magnesium stores, might be suffering from Bartter's syndrome type V, which is caused
by extreme gain of function mutations of the CASR. Identification of the known Bartter's type V
associated L125P mutation confirms the diagnosis, while identification of other ADH-causing mutations
or novel alteration(s) increase the likelihood of CASR mutation-related Bartter's syndrome, but do not
confirm it without additional family or functional studies. Absence of any mutations or the presence of
polymorphism(s) that are known to be functionally neutral makes the diagnosis very unlikely (see
Cautions for exceptions). See Parathyroid Disease and the Calcium-Sensing Receptor Gene (November
2005 Communique') in publications for additional information.
Reference Values:
Current as of January 4, 2013 7:15 pm CST 800-533-1710 or 507-266-5700 or MayoMedicalLaboratories.com Page 349