Hyperphosphatemia

Question: What proportion of their sons will have hyperphosphatemia? Hyperphosphatemia, a disease that causes abnormal bone growth and development, is inherited as an X-linked dominant trait. A woman who is heterozygous for the disease allele marries a normal man. What proportion of their sons will have hyperphosphatemia? What proportion of their daughters will have hyperphosphatemia? If hyperphosphatemia were an X-linked recessive trait, how would your answer differ?

Answer: Ok.... let's think this through. First we are given a disease caused by a dominant trait, where one parent (female) is heterozygous for the disease (and therefore has it), and her male companion is normal (doesn't have it.). We are told it's on the X chromosome. So, we concentrate on the female, and 1/2 of her children are going to "inherit" her X chromosome with the disease allele, and thus 1/2 of her daughters and sons will have the disease. Now if the allele for the disease were recessive, that would mean the parent (female) would not show the disease, and again, 1/2 of her children whether male or female would have that chromosome with the recessive allele. But now the situation is different. The mother is a carrier.... because she carriers a recessive disease causing allele, and therefore 1/2 of her daughters will also be carriers. As to her sons, again 1/2 of them will get the X chromosome with the disease allele, but because that son with the recessive trait does not have a corresponding spot on the Y chromosome for that gene, will show the disease. In sex-linked recessive traits, it only takes one allele in males (on the X chromosome) to show the disease.

Question: If hyperphosphatemia were an X-linked recessive trait, how would your answer differ? Hyperphosphatemia, a disease that causes abnormal bone growth and development, is inherited as an X-linked dominant trait. A woman who is heterozygous for the disease allele marries a normal man. What proportion of their sons will have hyperphosphatemia? What proportion of their daughters will have hyperphosphatemia? If hyperphosphatemia were an X-linked recessive trait, how would your answer differ?

Answer: 50% of the girls and 50%of the boys will have hyperphosphatemia. since the woman is heterozygous one of the alleles is the affected one and it will be passed on to half of the daughters (the other half receive the normal allele).In case of the boys,half of the boys receive the normal allele from their father. if the disease becomes recessive,none of the girls will be affected(recessive allele donot express in heterozygous condition) but again 50% of the boys affected.

Question: what causes hypercalcemia with hyperphosphatemia in the absence of renal failure?

Answer: Now thats an intresting question.. A few senarios that jump to mind are - a) Vitamin D intoxication: Remember Vit. D is a fat soluble vit. and can accumulate in the body. b) Granulomatous diseases like sarcoidosis..reason is that they cause an artificial state of vit.D excess due to synthesis of 1,25D3 by the macrophages in the granulomas. c) Blood malignancies- Myeloma would be the classical one but leukemia and lymphomas too. hypercalcemia is due to bone mets, synthesis of PTH like peptides while the high cell turnover (especially when on chemotherapy- tumor lysis) will cause hyperphospatemia. d) Solid tumors can also cause the above mentioned senarios for pretty much the same reasons. Hope that helps.