Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.

Recently, diagnostic criteria for preclinical Alzheimer's disease have been proposed. These describe and define three stages of disease. Stage I is focused on asymptomatic cerebral amyloidosis. Stage II includes evidence of synaptic dysfunction and/or early degeneration. Finally, stage III of the disease is characterized by the beginning of cognitive decline.

The Finnish type of familial amyloid polyneuropathy due to variant gelsolin is a rare form of familial amyloidosis. The subtype was first described in 1969 and is characterized by progressive cranial neuropathies, corneal lattice dystrophy and distal sensorimotor dysfunction. It is extremely uncommon, with only two families known to be affected in the UK. We discuss the case of a 70-year-old woman who presented with bilateral facial nerve palsies, bilateral sensorineural hearing loss and Finnish type familial hereditary amyloidosis. A literature search of the Medline database (1966–2005) was performed, using the keywords ‘amyloid’, ‘hearing loss’ and ‘facial palsy’; however, this association appears to be a novel finding. We review the current literature and discuss otorhinolaryngological presentations of amyloidosis.

Primary amyloidosis localized to the sinonasal tract is extremely rare with only 20 reported cases in the English literature. We describe a further case and review the literature.

The solution structure and stability of N-terminally truncated β2-microglobulin (ΔN6β2-m), the major modification in ex vivo fibrils, have been investigated by a variety of biophysical techniques. The results show that ΔN6β2-m has a free energy of stabilization that is reduced by 2.5 kcal/mol compared to the intact protein. Hydrogen exchange of a mixture of the truncated and full-length proteins at μM concentrations at pH 6.5 monitored by electrospray mass spectrometry reveals that ΔN6β2-m is significantly less protected than its wild-type counterpart. Analysis of ΔN6β2-m by NMR shows that this loss of protection occurs in β strands I, III, and part of II. At mM concentration gel filtration analysis shows that ΔN6β2-m forms a series of oligomers, including trimers and tetramers, and NMR analysis indicates that strand V is involved in intermolecular interactions that stabilize this association. The truncated species of β2-microglobulin was found to have a higher tendency to self-associate than the intact molecule, and unlike wild-type protein, is able to form amyloid fibrils at physiological pH. Limited proteolysis experiments and analysis by mass spectrometry support the conformational modifications identified by NMR and suggest that ΔN6β2-m could be a key intermediate of a proteolytic pathway of β2-microglobulin. Overall, the data suggest that removal of the six residues from the N-terminus of β2-microglobulin has a major effect on the stability of the overall fold. Part of the tertiary structure is preserved substantially by the disulfide bridge between Cys25 and Cys80, but the pairing between β-strands far removed from this constrain is greatly perturbed.

Amyloidosis of the upper aerodigestive tract is relatively rare. A case of localized amyloidosis involving all components of Waldeyer’s ring with added laryngeal involvement is described. This has not been previously reported. A literature review of this conditions is presented.

Both laryngocele and laryngeal amyloidosis are uncommon, and simultaneous occurrences of these entities are extremely rare. A case of laryngeal amyloidosis with laryngocele in which the computed tomography (CT) and magnetic resonance (MR) imaging of the larynx, clearly demonstrating both disease processes, is discussed. Diagnosis is confirmed by histopathologic specimens. Only two cases have been reported in the world literature, and this is the third case of laryngeal amyloidosis associated with laryngocele.

A case of giant amyloidoma in the left tonsil with extensive osseous metaplasia and a scanty and patchy monoclonal population of IgG Kappa plasma cells, is presented.

Localized tumoral amyloidosis is a rare, benign tumour of the upper aerodigestive tract. Organ-limited amyloidosis has been shown to be confined to various systems but, since the lesion was first described, only four cases situated in the tonsils have been reported in the English literature, and none of these had either osseous metaplasia or a monoclonal population of IgG Kappaplasma cells.

A case of primary amyloidosis of the external auditory canal is described. To the best of our knowledge this is the first case described in the literature.

Localized amyloidosis of the larynx is usually described as a non-bleeding lesion. We report a patient with localized laryngeal amyloidosis who developed a massive upper respiratory tract haemorrhage and died. This potentially fatal complication of localized amyloidosis of the larynx merits recognition as the disease could be controlled in most instances by surgical excision of the amyloid deposit.