biochem question I'm confused on

[Fungi121]

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This kaplan practice question basically had a patient present with physical sx of homocystinuria. Question asked which amino acid was most likely elevated...

I basically narrowed it down to either methionine (correct answer) or cystine (incorrect). But I couldn't choose because homocystinuria can be caused by deficiency in homocysteine methyltransferase (causing high cysteine) or deficiency in cystathionine synthase (causing high methionine). Is the latter just more common or something?

 

[ulikedaggers]

The most common form of homocystinuria is CBS deficiency, which results in increased methionine since homocysteine is now shunted towards methionine production. Are you sure the stem didn't hint at the exact cause? Did it mention B6 or B12 at all?

 

[alicealicealice]

This is a great point.
There are three types of homocystinuria, one for each of the enzymes, and they actually have different presentations.
Type I = most common = Cystathione synthase deficiency = most common = developmental delay, ectopia lentis, MR, marfanoid habitus, homocystinuria, hypocystienemia
Type II = defect in metyhylcobalamin formation = megaloblastic anemia, homocystinuria, hypomethioninemia
Type III = Methytetrahydrofolate reducatse = homocysteinuria, hypomethioninemia
Homocystinuria: A rare condition presenting as stroke and megaloblastic anemia
Lovell and Winter's Pediatric Orthopaedics - Google Books

For the purpose of the boards, it seems assume Type I especially given classic presentation as the others are exceeding rare and apparently do not have the same associated phenotype.
The one thing they all share is stroke risk

 

[ulikedaggers]

Also CBS deficiency can be a deficiency in the enzyme activity or in the enzyme's affinity for its cofactor, PLP. I'm pretty sure the sxs are the same, but obviously rx will be different.

 

[alicealicealice]

Yeah the small section in FA is good for going over what you restrict/give for the important subtypes.
Complete cystathione synthase deficiency = Give cysteine, restrict methionine (as your body will make more than enough from homocystiene), increase B12 and Folate (to promote conversion of homocystiene to methionine
Decrease affinity of cystathione synthase for pyridoxal phopshate cofactor (which uses B6) = Give B6 and cysteine
Homocysteine methyltransferase deficiency = Increase methionine

 

[acciddropping]

This kaplan practice question basically had a patient present with physical sx of homocystinuria. Question asked which amino acid was most likely elevated...

I basically narrowed it down to either methionine (correct answer) or cystine (incorrect). But I couldn't choose because homocystinuria can be caused by deficiency in homocysteine methyltransferase (causing high cysteine) or deficiency in cystathionine synthase (causing high methionine). Is the latter just more common or something?

There is a similar Q on UW but it also tells you that there is no methylB12 - so you can say that the synthesis of methionine is impaired.

 

[sazerac]

When homocystinuria leads to ectopic lentis, remember that it specifically dislocates down and in, vs Marfans which dislocates up and out.

I had a question once that presented with tall stature, long fingers, lens dislocated down, and you needed to presume a diagnosis to figure out the rest of the problem. Everybody assumed Marfans and went from there, but the correct answer followed from homocystinuria because the lens went down and in.

 

[sanj238]

When homocystinuria leads to ectopic lentis, remember that it specifically dislocates down and in, vs Marfans which dislocates up and out.

I had a question once that presented with tall stature, long fingers, lens dislocated down, and you needed to presume a diagnosis to figure out the rest of the problem. Everybody assumed Marfans and went from there, but the correct answer followed from homocystinuria because the lens went down and in.

is that really usmle testable.....

 

[ulikedaggers]

is that really usmle testable.....

It's in FC and FA. FC emphasizes it as an important distinction. FA mentions the direction of subluxation (for both), but doesn't make a direct comparison.

My guess is that a board question would give you at least 1 other hint to help you differentiate the two though.. like atherosclerosis vs aortic aneurysm, inheritance pattern, or mental ******ation/not.

homocystinuria = atherosclerosis, recessive, MR
Marfan = aortic aneurysms, dominant, no MR.

 

[alicealicealice]

It seems a little out there, but lens subluxation direction is repeated by Goljan, professors, etc. I guess its relevant because hypothetically 2 people could look the same but an ophthalmologic exam could help differentiate two completely different disease without any expensive testing. Most of the business of studying for this test is learning how to tell apart two things that can easily be confused. So just like blue sclera in OI is due to the visibility of choroidal veins, directionality of lens subluxation is one of those factoids worth remembering IMO.

 

[Transposony]

When homocystinuria leads to ectopic lentis, remember that it specifically dislocates down and in, vs Marfans which dislocates up and out.

I had a question once that presented with tall stature, long fingers, lens dislocated down, and you needed to presume a diagnosis to figure out the rest of the problem. Everybody assumed Marfans and went from there, but the correct answer followed from homocystinuria because the lens went down and in.

The way I remember it is that in:

Marfan's: you are looking up @ Mars since you are Mar's Fan.

Homocystinuria: you are looking down since you are peeing out homocysteine.

 

[Transposony]

I see two potential questions on this topic (with or without the direction of lens subluxation):

1. They'll give you up/down arrow question asking to pick up the levels of methionine,  homocysteine, Cystathionine, cysteine in blood and/or urine.

2. Another up/down arrow questions asking to pick up the best dietary modification: methionine,  cysteine,  B6 / B12 / folate.

 

[sanj238]

It's in FC and FA. FC emphasizes it as an important distinction. FA mentions the direction of subluxation (for both), but doesn't make a direct comparison.

My guess is that a board question would give you at least 1 other hint to help you differentiate the two though.. like atherosclerosis vs aortic aneurysm, inheritance pattern, or mental ******ation/not.

homocystinuria = atherosclerosis, recessive, MR
Marfan = aortic aneurysms, dominant, no MR.

if its in FA and I havent read biochem FA yet, then its pretty much testable, thanks for the heads

 

[sanj238]

The way I remember it is that in:

Marfan's: you are looking up @ Mars since you are Mar's Fan.

Homocystinuria: you are looking down since you are peeing out homocysteine.

i will never forge tthis. thanks.

 

[sazerac]

I see two potential questions on this topic (with or without the direction of lens subluxation):

1. They'll give you up/down arrow question asking to pick up the levels of methionine,  homocysteine, Cystathionine, cysteine in blood and/or urine.

2. Another up/down arrow questions asking to pick up the best dietary modification: methionine,  cysteine,  B6 / B12 / folate.

It would be funny to get an up/down arrow question and one of the columns is "lens dislocation direction".

 

[Transposony]

It would be funny to get an up/down arrow question and one of the columns is "lens dislocation direction".

Nah............that would be like giving it to you on a plate.