Question

Familial amyloidotic polyneuropathy is due to amyloidosis of nerves caused by deposition of

• A. Amyloid associated protein
• B. Mutant calcitonin
• C. Mutant transthyretin
• D. Normal transthyretin

Hint:

Inherited ATTR amyloidosis comes from a mutant transthyretin gene, not the normal protein.

Answer 1

The Correct Option is C

This question checks which abnormal protein builds up in the nerves in familial amyloidotic polyneuropathy, an inherited amyloid disease.

1. Amyloid associated protein: This protein builds AA amyloid, seen with long-standing inflammatory disease like rheumatoid arthritis or chronic infection, and it mostly affects the kidney and spleen, not an inherited nerve disease.
2. Mutant calcitonin: Calcitonin is not an amyloid-forming protein in this condition, it is unrelated to familial amyloidotic polyneuropathy.
3. Mutant transthyretin: Transthyretin is a liver-made protein that carries thyroid hormone and vitamin A in blood. An inherited point mutation makes it unstable, so it misfolds and deposits as amyloid fibrils in peripheral nerves. This exactly matches familial amyloidotic polyneuropathy.
4. Normal transthyretin: Non-mutant transthyretin can also form amyloid, but only in old age, as senile systemic amyloidosis affecting the heart, this is a different, non-familial condition.

Because the disease is inherited and nerve-specific, the responsible protein has to be the abnormal, mutant form of transthyretin, not the normal protein or another amyloid precursor.

Let's summarize:

• AA amyloid comes from amyloid associated protein and is linked to chronic inflammation.
• Senile systemic amyloidosis comes from normal transthyretin and affects the heart in old age.
• Familial amyloidotic polyneuropathy comes from mutant transthyretin depositing in nerves.

So the correct answer is mutant transthyretin.