Talk:Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency

note

What does this realy mean ? I've heard of it but dont realy understand the stituation which a sufferer is faced with. What restrictions does it bring and what is diffrent physicaly?

The article actually contains the answers to your questions, but is built on the foundation of the basic congenital adrenal hyperplasia article. This particular type (17OH) is a very rare form that is hardly ever referred to in the popular media. In the congenital adrenal hyperplasia article are links to simpler internet explanations of CAH, like the patient education material from Johns Hopkins Hospital. alteripse 22:39, 6 May 2006 (UTC)

question

HI; I am interested in this condition.

Is it always autosomal recessive? or would 'carriers' have reduced activity/expression of 17 alpha hydroxylase?

I would like to know if anyone has case experience of an infant mistaken to have PAIS, when the real issue is 17 alpha hydroxylase deficiency? Would anyone care to comment on what could happen to an individual given large doses of testosterone and HcG as an infant over time?

I also wonder that in such a case would natural surges in gonadotrophins over time give the enzyme some activity, both by gonadotrophins increasing the enzymes activity, and once testosterone is present at a reasonable level would it induce extra expression of 17 alpha hydroxylase to compensate for it's lack of activity?

I have read of a large variety of phenotypes for this condition. One thing I am interested in particular is, the example of an XY individual who is give testosterone and growth hormone to treat genital ambiguity... Recent literature has suggest that increased 17 alpha hydroxylase enzyme levels can increase the production of things like TNF alpha dramatically. Couldn't that be dangerous? Would it really be sensible to maintain a course of testosterone throughout life given this? User:nic@sounddesign.co.nz 11:43, 21 April 2007 (NZ time) cheers if anyone could offer any insights, Nic. nic@sounddesign.co.nz

Hi to NZ. Note that all the following answers are speculation, not medical advice.

Always recessive? Short answer: all reported cases of the disease have been autosomal recessive. Long answer: As the gene is on chromosome 10 and codes for an enzyme (so that everyone has two copies), one would predict that both copies of the gene would have to be defective to produce any detectable disease. There are few examples of dominant disease caused by mutations of single genes for enzymes. None of the described cases in which genotyping was performed were due to defects of only a single gene. None of the handful of reported families demonstrated a dominant inheritance pattern. There are no clinically detectable effects in those who carry only a single gene of the more common forms of CAH. However, although there is no disease caused by having a single copy, it is possible that mildly reduced enzyme activity in adrenal or gonadal tissue could be demonstrated, since it is possible to have a mild reduction of an enzyme activity without it causing any problems.

Mistaken for PAIS? As mentioned in the article, severe 17OH CAH occurring in a genetic male could easily be mistaken for PAIS in infancy.

Thank you for your promt response, I really appreciate it.

Testosterone/hCG effects? Administered testosterone effects are difficult to quantify in infants, and androgen receptor testing has only recently become available. If an infant with this condition were given standard infant doses of testosterone and hCG (as is often done in the evaluation or treatment of XY infants with ambiguity), one would predict a normal response because there is no defect of tissue responsiveness or 5α-reduction. No risk is known for this treatment. I am not sure what you mean by "given large doses over time". If testosterone is given for a prolonged period, one would expect to see appearance of pubic hair and acceleration of growth and bone maturation, similar to that seen with untreated non-saltwasting 21OH CAH. Standard therapeutic hCG courses are typically about 5 weeks, and no harm is known to occur to normal testes. If you aren't asking about ten times that much, maybe nothing detectable would happen.

Actually funny you should mention it I was talking about ten times the amount of testosterone administered to an infant. 250 units (I can't remember the particular unit sorry), as opposed to the more standard 25 units give three times.

Would this enhance 17OH activity? Testosterone is not known to induce the enzyme. hCG might induce the enzyme to some degree, but not permanently. Part of the problem in imagining treatment with hCG is that after a baby is born, more testosterone or hCG will not fix ambiguity, just make the penis a little bigger. At puberty, these people have high LH levels. Since LH and hCG are quite similar in their effects and act on the same receptors, it is difficult to think of any reason to keep giving hCG to an adolescent or adult male with this condition. Their sensitivity to testosterone is normal, and that would be the best post-pubertal treatment for this impairment of testosterone synthesis.

Would testosterone treatment be dangerous? Don't confuse replacing a deficient hormone with giving unnaturally high amounts. If the doses are normal replacement doses for a male with impaired ability to make testosterone, there is no known harm compared to normal male disease susceptibility. If a man with a severe form of this condition did not take testosterone for most of his adult life, one would expect osteoporosis, poor muscle maintenance, diminished libido and energy. alteripse 18:34, 21 April 2007 (UTC)

compound heterozygous

I note a recent case in the literature describing a compound heterozygous polymorphism causing 17 hydroylase deficiency

That means that the two CYP17 genes had two different mutations, not an unusual finding in all the forms of CAH, since they are recessive enzyme deficiencies. alteripse 12:10, 19 May 2007 (UTC)

I have only read of one compound heterozygote for CAH. Are you sure it's so common? Thanks for your comments alterpise. I have ascertained (at least in my case) that my LH theory doesn't hold true. Nic Nic 00:07, 12 June 2007 (NZ time)