Familial Amyloidotic
Polyneuropathy (FAP)

Case Study A
A 62-year-old man developed burning and numbness of the feet and ankles, followed by pins and needles in the fingers. Surgical release of the right carpal tunnel and exploration of the right elbow produced no relief. At sixty-three, he developed impotence. Early the next year he noted weakness of the hands and began to experience sharp pains radiating from the hands to the forearms. He then became aware of spontaneous twitching of arm and leg muscles and volitional cramping of muscles in the forelegs, particularly at night. Walking became unsteady because of weakness and orthostatic dizziness. There was no family history of neuropathy. He had no history of diabetes.

At sixty-five years, his physical examination revealed atrophy of the hand intrinsic muscles and weakness of the flexors of the fingers and wrists. Pin prick sensation was markedly diminished in the distal extremities. Vibration and position senses were minimally reduced in the feet. Deep tendon reflexes were absent in the lower extremities. Numerous normal studies included: blood count, sedimentation rate, thyroxine, renal and liver function tests, vitamin B12 and folate, serological testing for syphilis, immunoprotein electrophoresis, and 24 hour urine for Bence Jones protein, mercury, lead, arsenic, or thallium. A random blood sugar was 146mg/dl. Chest x-ray revealed borderline heart enlargement. The EKG showed complete right bundle block with left axis deviation. A sural nerve biopsy demonstrated the presence of amyloid.

Serum molecular DNA testing documented a substitution of methionine for valine at position thirty of the transthyretin gene resulting in a diagnosis of amyloidosis.