A 3-year-old boy has a mutation in the calcium receptors on

Discussion in 'USMLE STEP 1' started by Neeraj., Oct 6, 2008.

  1. Neeraj.

    Neeraj. Guest

    A 3-year-old boy has a mutation in the calcium receptors on cell surfaces of his parathyroid gland and on the basolateral (blood) side of the thick ascending limb of the loop of Henle. Which of the following patterns is expected with a mutation that leads to activation of this receptor in the absence of binding of its ligand?

    Ca++ Parathyroid hormone Urine calcium

    A ) Hypercalcemia high high

    B ) Hypercalcemia high low

    C ) Hypercalcemia low high

    D ) Hypercalcemia low low

    E ) Hypocalcemia high high

    F ) Hypocalcemia high low

    G ) Hypocalcemia low high

    H ) Hypocalcemia low low
  2. Pranjal.

    Pranjal. Guest

    I thought it was B and was typing a long explanation and then I reread the question and changed my mind. It is the calcium receptor ON the PT gland that is mutated and in a state of activation. So what it is doing is causing feedback inhibiton because the PT gland is tricked into thinking their is a ton of calcium. So that means you can become hypocalcemic (piss out all your calcium) and your body will not release PTH because it thinks their is alot of calcium so low PTH. Since PTH also acts in the early DCT to reabsorb calcium, the calcium will stay in the urine get excreted so high calcium in the urine.

    I go with G.
  3. Guest

    Guest Guest

    The right ans: B

    Case is FAMILIAL HYPERCALCEMIC HYPOCALCIURIA--MOSSTLY AUTOSOMAL DOM,ASYMPTOMATIC.....BUT daignosis is need to prevent overenthusiastic surgeon from nipping away the PTH glands thinking them to b the cause of hypercalcemia

    Clinical Presentation of FHH
    Hypercalcemia
    Hypocalciuria
    Normal to high levels of PTH
    Hypermagnesemia

    The calcium-sensing receptor regulates the secretion of parathyroid hormone in response to changes in extracellular calcium concentrations, and mutations that result in a loss of function of the receptor are associated with familial hypocalciuric hypercalcemia.

    Familial Hypocalciuric Hypercalcemia (FHH) is also known as Familial Benign Hypercalcemia because it is generally asymptomatic
    FHH is easily confused with milder cases of the more common primary hyperparathyroidism

    Most cases of FHH are associated with loss-of-function mutations in a single gene (CASR),Genetic testing for FHH-associated mutations in CASR can help to prevent unnecessary and inappropriate parathyroidectomy in patients with FHH

    The vast majority of FHH is caused by autosomal dominant loss-of-function mutations in the gene CASR, which codes for the calcium-sensing receptor (CASR). CASR is a G-protein coupled membrane receptor expressed in the parathyroid glands and the kidneys, among other tissues

    In the parathyroid glands, CASR mediates the feedback inhibition of parathyroid hormone release in response to a rise in the blood calcium concentration. Loss-of-function mutations in CASR impair the feedback inhibition of parathyroid hormone secretion in response to a rise in the blood calcium concentration. Thus, higher than normal blood calcium levels are necessary to inhibit release of parathyroid hormone, resulting in hypercalcemia associated with inappropriately normal or mildly elevated levels of parathyroid hormone. The degree of hypercalcemia depends on how severely the mutation affects the function of the CASR molecule.

    In the kidneys, CASR is involved in the feedback inhibition of parathyroid hormone-independent calcium reabsorption. Loss-of-function mutations in CASR prevent feedback inhibition of calcium reabsorption in response to a rise in the blood calcium concentration. Since calcium continues to be efficiently reabsorbed despite hypercalcemia, the calcium concentration in the urine is unexpectedly low relative to the calcium concentration in the blood (relative hypocalciuria).

    Diagnosis of FHH

    Hypercalcemia
    Calcium/creatinine clearance ratio <0.01
    Hypercalcemic infant/child in family
    Genetic testing for mutations in CASR
    FHH is considered in individuals with asymptomatic persistent hypercalcemia accompanied by inappropriately normal or mildly elevated blood levels of parathyroid hormone. Differentiation from primary HPT can often be achieved by measuring the renal calcium/creatinine clearance ratio, which generally is less than 0.01 in patients with FHH and higher in patients with primary HYPERPARATHYROIDISM
  4. Guest

    Guest Guest

    "a mutation that leads to activation of this receptor", not loss-of-function...isn't it????

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