subacute combined degeneration

[MudPhud20XX]

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Kaplan nuero explains that subacute combined degenration is seen most commonly in cases of vitamin B12 def, sometimes related to pernicious anemia. It says that the disases is characterized by patchy losses of myelin in the dorsal columns and lateral corticospinal tracts, but doesn't explain the mechanism.

What does B12 def have to do with demyliniation? Is this some kind of auto immune related disease that auto antibodies attaking not only the parietal cells but also the myelins in the CNS?

Many thanks in advance.

 

[MDcaffeineRequired]

Accumulation of Methylmalonic Acid caused by the B12 deficiency is what damages the nerves. B12 is required to change Methylmalonic Acid to Succinyl CoA.

 

[Psai]

What does b12 do? It helps folate to turn homocysteine into methionine so that you can methylate stuff with sam like making dna or epinephrine
But say you're breaking down odd chain fatty acids or isoleucine/valine. What do you get? Propionyl coa. How do you get rid of it? You do a whole bunch of reactions that put it into the tca cycle. when you're trying to put propionyl coa into the krebs cycle, you have propionyl coa into methylmalonyl coa into succinyl coa (tca intermediate). methylmalonyl-coa mutase turns methylmalonyl coa into succinyl coa. what is the coenzyme for that mutase? b12 (absorbed in the terminal ileum with intrinsic factor). no b12 for whatever reason, no r-factor, crohns, pernicious anemia, poor diet, zollinger ellison with low gastric ph, etc. can lead to buildup of methylmalonyl coa and propionyl coa.

So if you can't break down these intermediates, you get buildup of propionyl coa and methylmalonyl coa. Propionyl coa builds up and replaces acetyl coa in neuronal membranes which results in demyelination. Also methylmalonyl coa is toxic to schwann cells which myelinate peripheral nerves. Source: goljan. demyelinate posterior column -> lose proprioception and vibratory sense. lateral cortical spinal tract loss -> umn lesion (spastic, positive babinski with toes up). you also get dementia (reversible cause of dementia along with hypothyroidism so you measure b12 and tsh)

 

[MudPhud20XX]

Accumulation of Methylmalonic Acid caused by the B12 deficiency is what damages the nerves. B12 is required to change Methylmalonic Acid to Succinyl CoA.

Dang, that's heavy. Thanks a lot! Wait so is this related to the methylmalonic aciduria that gives rise to "peripheral neuropathy?"

 

[MudPhud20XX]

What does b12 do? It helps folate to turn homocysteine into methionine so that you can methylate stuff with sam like making dna or epinephrine
but say you're breaking down odd chain fatty acids or isoleucine/valine. what do you get? propionyl coa. how do you get rid of it? you do a whole bunch of reactions that put it into the tca cycle. when you're trying to put propionyl coa into the krebs cycle, you have propionyl coa into methylmalonyl coa into succinyl coa (tca intermediate). methylmalonyl-coa mutase turns methylmalonyl coa into succinyl coa. what is the coenzyme? b12 (absorbed in the terminal ileum). no b12 for whatever reason, crohns, pernicious anemia, poor diet, zollinger ellison with low gastric ph, etc. can lead to buildup of methylmalonyl coa.

So if you can't break down these intermediates, you get buildup of propionyl coa and methylmalonyl coa. Propionyl coa builds up and replaces acetyl coa in neuronal membranes which results in demyelination. Also methylmalonyl coa is toxic to schwann cells. Source: goljan. demyelinate posterior column -> lose proprioception and vibratory sense. lateral cortical spinal tract loss -> umn lesion (spastic, positive babinski with toes up). you also get dementia (reversible cause of dementia along with hypothyroidism so you measure b12 and tsh)

Yup makes sense! Thanks!