Amyloidosis

Question 1

What is amyloidosis

Answer 1

Group of disorders characterised by extracellular deposits of a protein in abnormal fibrillar form, resistant to degradation

Question 2

In which conditions is amyloid deposition a feature?

Answer 2

Alzheimer’s
T2DM
Haemodialysis related amyloidosis

Question 3

List the 3 types of amyloidosis

Answer 3

AL amyloid (primary)
AA amyloid (secondary)
Familial amyloidosis

Question 4

Describe the pathophysiology of AL amyloid (primary amyloidosis)

Answer 4

Proliferation of plasma cell clone
Amyloidogenic monoclonal immunoglobulins
Fibrillar light chain protein deposition
Organ failure
Death

Question 5

What diseases is primary amyloidosis associated with

Answer 5

Myeloma
Waldenstrons
Lymphoma

Question 6

What organs are involved in primary amyloidosis. Describe how

Answer 6

Kidneys - glomerular lesions - proteinuria and nephrotic syndrome
Heart - restrictive cardiomyopathy, arrhythmias, angina
Nerves - peripheral and autonomic neuropathy - carpal tunnel syndrome
Gut - macroglossia, malabsorption, weight loss, perforation, haemorrhage, obstruction, hepatomegaly
Vascular - purpura, especially periorbital

Question 7

How is primary amyloidosis treated?

Answer 7

Optimise nutrition, PO melphalan and prednisolone extends survival. High does melphalan with autologous stem cell transplant may be better

Question 8

Describe AA amyloid (secondary amyloidosis)

Answer 8

Amyloid derived from serum amyloid A (acute phase protein) reflecting chronic inflammation (RA,IBD,TB, bronchiectasis, osteomyelitis)
Affects kidneys, liver and spleen - proteinuria, hepatomegaly and nephrotic syndrome

Question 9

How is secondary amyloidosis treated?

Answer 9

Manage the underlying condition optimally

Question 10

How is fmailial amyloidosis inherited?

Answer 10

Autosomal dominant

Question 11

Describe familial amyloidosis

Answer 11

Mutations in transthyretin (transport protein produced by the liver)
Causes a sensory or autonomic neuropathy with renal and cardiac involvement

Question 12

How can familial amyloidosis be cured?

Answer 12

Liver transplant

Question 13

How is familial amyloidosis diagnosed?

Answer 13

Biopsy of affected tissue (rectum and sc fat) and positive congo red staining with apple-green birefringence under polarized light microscopy

Question 14

What is the median survival of familial amyloidosis

Answer 14

1-2 years. Patients with myeloma too have decreased survival