Peripheral neuropathy in cobalamin deficiency

[alternatego]

---

Members don't see this ad.

In megaloblastic anemia caused by cobalamin deficiency, is subacute combined degeneration caused by accumulation of propionyl CoA or methylmalonic acid? My sources do not agree with each other :S

 

[WonderBoy]

Methylmalonic according to pathoma.

 

[alternatego]

Methylmalonic according to pathoma.

that's precisely the issue, Pathoma says methylmalonic, but RR Path says propionyl CoA replaces acetyl CoA in the neuron's cell membrane, disrupting myelination.

 

[Myxedema]

Robbins PBOD, 8th Edition:

The neurologic complications associated with vitamin B12 deficiency are more enigmatic, since they are not improved by folate administration. The other known reaction that depends on vitamin B12 is the isomerization of methylmalonyl coenzyme A to succinyl coenzyme A, which requires adenosylcobalamin as a prosthetic group on the enzyme methylmalonyl–coenzyme A mutase. A deficiency of vitamin B12 thus leads to increased plasma and urine levels of methylmalonic acid. Interruption of this reaction and the consequent buildup of methylmalonate and propionate (a precursor) could lead to the formation and incorporation of abnormal fatty acids into neuronal lipids. It has been suggested that this biochemical abnormality predisposes to myelin breakdown and thereby produces the neurologic complications of vitamin B12 deficiency (Chapter 28). However, rare individuals with hereditary deficiencies of methylmalonyl–coenzyme A mutase, while having complications related to methylmalonyl acidemia, do not suffer from the neurologic abnormalities seen in vitamin B12 deficiency, casting doubt on this explanation.

So accumulation of both can be associated with neurologic symptoms.