Amyloidosis - Metabolic disorders

Metabolic disorders

Amyloidosis

Definition

Amyloidosis refers to the extracellular deposition of fibrils composed of low-molecular-weight proteins, many of which circulate as constituents of plasma.

Aetiology/pathophysiology

At least 21 different protein precursors of amyloid fibrils are now known (see Table 13.2).

Besides systemic amyloid deposition, organ specific amyloid may occur in the skin or heart and most notably in the brain in Alzheimer’s disease. Genetic factors may be involved in predisposing to the development of fibrillogenesis and amyloidosis:

·        Genetic mutations resulting in proteins with increased propensity to form fibrils.

·        Genetic polymorphisms in protein subunits and cofactors.

·        Inherited disorders with chronic inflammation.

Clinical features

The precursor protein, the tissue distribution and the amount of amyloid deposited affect the clinical presen-tation. The kidneys, heart and liver are often affected.

·        Renal amyloid deposition: asymptomatic proteinuria or nephrotic syndrome, deposition in blood vessels or tubules causes renal failure.

·        Cardiac amyloid deposition leads to disorders of contractility and heart failure, arrhythmia and heart block. Deposition in the coronary arteries can lead to ischaemic heart disease.

·        Gastrointestinal system: hepatomegaly, splenomegaly, gastrointestinal bleeding and dysmotility.

·         Nervous system: various peripheral and autonomic neuropathies may occur. Central nervous system deposition is rare in systemic amyloid; however, organ specific CNS deposition is seen in Alzheimer’s disease.

·        Musculoskeletal system deposition may cause muscle pseudohypertrophy, macroglossia, arthropathy, spondyloarthropathy, bone disease and carpal tunnel syndrome. This form of deposition is particularly seen in dialysisassociated amyloid.

·        Skin deposition causes a waxy thickening and easy bruising.

Investigations

Where possible biopsy and histology is used to confirm clinical suspicion. Amyloid appears as homogenous substance that stains pink on haematoxylin and eosin and stains red with Congo red.

Management

Therapy is aimed at the underlying cause where possible such as inflammation, infection or blood dyscrasia. Differing manifestations such as renal failure require support. In the hereditary amyloidoses where the precursor protein is produced by the liver, liver transplantation is curative.