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

Step 1: Understanding the Question:
Familial amyloidotic polyneuropathy is an inherited disease where amyloid deposits build up in peripheral nerves. We need to identify which protein forms these deposits.

Step 2: Key Formula or Approach:
Amyloid disease is named by the precursor protein that misfolds and deposits as amyloid fibrils. AA amyloidosis comes from serum amyloid associated protein, AL amyloidosis comes from immunoglobulin light chains, and ATTR amyloidosis comes from transthyretin, a transport protein made in the liver that normally carries thyroxine and retinol.

Step 3: Detailed Explanation:
In the inherited form, a point mutation in the transthyretin gene changes the protein's shape so it misfolds easily and deposits as amyloid fibrils in peripheral nerves, this is called familial amyloidotic polyneuropathy or hereditary ATTR amyloidosis.
Amyloid associated protein forms AA amyloidosis, which is linked to chronic inflammatory disease and mainly deposits in the kidney, liver, and spleen, not primarily in nerves as an inherited disease.
Mutant calcitonin is not a recognised amyloid precursor, calcitonin itself is not implicated in this disease, though calcitonin levels are checked in medullary thyroid cancer for an unrelated reason.
Normal, unmutated transthyretin can deposit as amyloid too, but that happens in old age as senile systemic amyloidosis, mainly affecting the heart, it is not the familial nerve disease, which specifically needs a mutant form of the protein.

Step 4: Final Answer:
Familial amyloidotic polyneuropathy is caused by deposition of mutant transthyretin.