CGD vs. MPO deficiency

[dbeast]

Quote from Uworld:

"The difference between CGD and MPO deficiency lies in the fact that in CGD some phagocytosed organisms can be killed because these organisms produce their own hydrogen peroxide which myeloperoxidase then uses to produce free radicals. In myeloperoxidase deficiency, the enzyme myeloperoxidase is absent, so both catalase positive and catalase negative organisms will survive within phagocytes."

I *thought* that CGD patients were particularly susceptible to catalase positive infections like staph... Could be wrong tho.

Also, the wikipedia school of medicine (where I'm getting my other degree) says that MPO deficiency is generally less severe than CGD, which makes no sense based on the above explanation. Can anybody clarify this situation? Thank you mucho!

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[bangarang]

Quote from Uworld:

"The difference between CGD and MPO deficiency lies in the fact that in CGD some phagocytosed organisms can be killed because these organisms produce their own hydrogen peroxide which myeloperoxidase then uses to produce free radicals. In myeloperoxidase deficiency, the enzyme myeloperoxidase is absent, so both catalase positive and catalase negative organisms will survive within phagocytes."

I *thought* that CGD patients were particularly susceptible to catalase positive infections like staph... Could be wrong tho.

Also, the wikipedia school of medicine (where I'm getting my other degree) says that MPO deficiency is generally less severe than CGD, which makes no sense based on the above explanation. Can anybody clarify this situation? Thank you mucho!

The bolded part sounds wrong.

First, know bacteria form H2O2 as a byproduct of metabolism.

CGD with catalase-positive: NADPH oxidase deficiency > no superoxide > H2O2 builds up > catalase-positive survives because it breaks down H2O2 before it gets converted to HOCl by MPO
CGD with catalase-negative: NADPH oxidase deficiency > no superoxide > H2O2 builds up > catalase-negative can't break it down > MPO converts it to HOCl and kills it

MPO deficiency: NADPH oxidase still intact > regular killing (pts. usually asymptomatic except for increased risk of Candidal infections). O2-dependent killing is more effective than O2-independent killing, so MPO deficiency is less severe (per Pathoma).

Edit: We're posting a lot of study questions and confusing topics in "Step I Complicated Concepts" in an effort to minimize all of the short threads. Just FYI!

 

[dbeast]

The bolded part sounds wrong.

First, know bacteria form H2O2 as a byproduct of metabolism.

CGD with catalase-positive: NADPH oxidase deficiency > no superoxide > H2O2 builds up > catalase-positive survives because it breaks down H2O2 before it gets converted to HOCl by MPO
CGD with catalase-negative: NADPH oxidase deficiency > no superoxide > H2O2 builds up > catalase-negative can't break it down > MPO converts it to HOCl and kills it

MPO deficiency: NADPH oxidase still intact > regular killing (pts. usually asymptomatic except for increased risk of Candidal infections). O2-dependent killing is more effective than O2-independent killing, so MPO deficiency is less severe (per Pathoma).

Edit: We're posting a lot of study questions and confusing topics in "Step I Complicated Concepts" in an effort to minimize all of the short threads. Just FYI!

Thanks for the help, I knew something from Uworld sounded wrong. So... now I'm gonna get a little abstract. Considering MPO contains a heme pigment (giving pus/sputum its green color, yes I got a question on this), do you think an MPO deficient patient would never have green sputum? I feel like I could see this coming up on the real test for some reason.

 

[bangarang]

Thanks for the help, I knew something from Uworld sounded wrong. So... now I'm gonna get a little abstract. Considering MPO contains a heme pigment (giving pus/sputum its green color, yes I got a question on this), do you think an MPO deficient patient would never have green sputum? I feel like I could see this coming up on the real test for some reason.

I think that depends on the nature of the mutation (i.e., deficiency or abnormal gene product). That's a pretty good concept though.

 

[bangarang]

MPO deficiency: NADPH oxidase still intact > regular killing (pts. usually asymptomatic except for increased risk of Candidal infections). O2-dependent killing is more effective than O2-independent killing, so MPO deficiency is less severe (per Pathoma).

Clarification: both NADPH oxidase and MPO pathways are O2-dependent killing; the O2-independent pathways are like lysozymes in macrophages and major basic protein from eosinophils.

 

[dntoupin]

With the correction of the previous post (production of HOCl is O2-dependent, not O2-independent), why then is MPO deficiency less severe than CGD? Are we to assume simply that HOCl is not as important as superoxide/hydrogen peroxide in the killing of microorganisms within leukocytes?

 

[Locrian]

With the correction of the previous post (production of HOCl is O2-dependent, not O2-independent), why then is MPO deficiency less severe than CGD? Are we to assume simply that HOCl is not as important as superoxide/hydrogen peroxide in the killing of microorganisms within leukocytes?

Because there are 3 species that can be generated which are bactericidal.

1. The Superoxide Radical is directly Bacteriacidal
2. The Superoxide Radical may be acted on by SOD --> H202 which (normally) can generate HOCL (Bactericidal)
3. H202 can still be converted to the hydroxyl free radical via the fenton reaction with is also directly bacteriacidal.

MPO deficiency knocks out only 1 of the 3 species generated for killing.

Also, the Hydroxyl free radical is more reactive then the superoxide.
So catalase positive bacteria are more resistant to killing by neutralizing the H2O2 that could still utilized in the Fenton reaction.
Catalase negative have no increased resistance, just in the presence of MPO deficiency are too less effectively killed, as HOCL is better then OH.

"The difference between CGD and MPO deficiency lies in the fact that in CGD some phagocytosed organisms can be killed because these organisms produce their own hydrogen peroxide which myeloperoxidase then uses to produce free radicals. In myeloperoxidase deficiency, the enzyme myeloperoxidase is absent, so both catalase positive and catalase negative organisms will survive within phagocytes."

I *thought* that CGD patients were particularly susceptible to catalase positive infections like staph... Could be wrong tho.

Yes... you simply restated the same thing the answer was trying to convey...

" in CGD some phagocytosed organisms can be killed because these organisms produce their own hydrogen peroxide which myeloperoxidase then uses to produce free radicals."
...If the organism generates H202, but is also catalase positive...
...they are less efficiently killed because they neutralize the H2O2 they produce before MPO can act on it...
...thus CGD are susceptible to catalase positive infections just like you said.

 

[Polycherry]

can be killed because these organisms produce their own hydrogen peroxide

Why would organisms even produce their own H2O2? What is the logic behind this? Even in the lab catalase test we add H2O2 to the colony..

Robbins says, the superoxide produced by NADPH oxidase turns to H2O2 naturally without the need of any enzyme. So in the absence of NADPH oxidase, how can H2O2 arise?