Amyloidosis

Question 1

Define amyloidosis

Answer 1

The accumulation of misfolded proteins known as amyloid in organs and tissues

Classification:

1. Primary Amyloidosis/ Immunoglobulin Light Chain Amyloidosis (AL)
   - Kidney heart nerves gut vascular
2. Secondary Non-familial Amyloidosis (AA) – Serum amyloid A
   - Kidney liver and spleen
3. Familial Amyloidosis (Transthyretin associated, ATTR),
   - Autonomic neuropathy ± renal/cardiac involvement

Question 2

What are the causes/risk factors of amyloidosis?

Answer 2

AL amyloid – most common type; insoluble monoclonal Ig light chain or light chain
fragments produced by plasma cells; deposits in kidney, heart and nerves (vasa nervorum)
• MGUS
• Multiple myeloma

AA amyloid – soluble serum amyloid A (SAA) protein (a major acute-phase reactant
protein) is deposited in the extracellular space as insoluble fibrils; occurs in chronic
inflammatory disease; deposits in kidney, GI tract and thyroid
• Inflammatory polyarthropathies e.g. RA, psoriatic arthritis, ankylosing spondylitis
• Chronic infections e.g. bronchiectasis, TB, osteomyelitis
• IBD – Crohn’s
• Malignancy e.g. Hodgkin’s lymphoma, renal cell carcinoma

Familial Amyloidosis, ATTR - Autosomal dominant.
• Most commonly due to a mutation in the Transthyretin gene (TTR) - tetrameric transport protein which transports Thyroxine and Retinol-binding protein.

Other mutations include: 
• Apoprotein A-I 
• Gelsolin 
• Lysozyme 
• Fibrinogen Aα

Question 3

What are the signs and symptoms of amyloidosis?

Answer 3

Cardiomyopathy/heart failure
• Fatigue
• Weight loss
• SOBOE
• Raised JVP
• Oedema
• Postural hypotension

GI involvement
• Nausea
• Abdominal cramps
• Change in bowel habit
• Weight loss
• Hepatomegaly
Nephrotic syndrome
• Fatigue
• Oedema
• Postural hypotension

Neurological
• Peripheral neuropathy
(paraesthesia)
• Autonomic neuropathy
(bladder/bowel dysfunction)
• Carpal tunnel syndrome

Other
• Periorbital purpura/eyelid
petechiae (raccoon eyes)
• Macroglossia (AL only)
• Shoulder pad sign (enlarged
shoulders)

Question 4

What investigations are carried out for amyloidosis?

Answer 4

• Tissue Biopsy - amyloid Positive: Green birefringence when stained with Congo red.
• Immunofixation - serum or Urine. Monoclonal proteins are pr esent in AL.
• Immunoglobulin free light chain assay - abnormal kappa to lambda ratio in AL.
• Mass Spectroscopy - confirms protein type
• Genetic Testing - positive mutations in familial amyloidosis.
• Urinalysis - proteinuria
• Bloods - FBC, U&E, LFTs, CRP, Coagulation screen
• ECG - arrhythmia
• Echo - heart dysfunction and amyloid speckles. Signs of CCF