A second case of liraglutide-type localised amyloidosis.

Abstract

Amyloidosis is characterised by extracellular deposition of proteinaceous fibrils, disrupting tissue structure and function. There are at least 36 different types of amyloid, and correct identification of the specific amyloid precursor protein is of paramount importance, as therapy varies dramatically depending on the amyloid type. The most common amyloid types encountered in peripheral nerves are AL (immunoglobulin light chain) and ATTR (transthyretin) [1]. Iatrogenic amyloidosis is a form of localised amyloidosis, caused by the repetitive injection of protein medications, such as insulin [2]. A 78-year-old male, with a history of well-controlled diabetes mellitus, presented with a 30-year history of bilateral foot soreness and numbness. Six months prior to the presentation, he developed intermittent burning and a hot/cold sensation in his feet which spontaneously improved. He also reported a 15-year history of nonradiating low back pain. He had no weakness, weight loss, orthostatic light-headedness, or bowel or bladder dysfunction. Other family members have reported similar sensory symptoms. Neurological examination was remarkable for decreased pinprick sensation from the mid-shin down to the toes, and mildly decreased hot temperature sensation in the right foot. Reflexes were decreased at the right patella, absent at the left patella and bilateral ankles. Motor and gait examination were normal. Nerve conduction studies/electromyography demonstrated mild bilateral old or chronic L5 radiculopathies with no evidence of ongoing denervation, and no evidence of a large fibre peripheral neuropathy. Thermoregulatory sweat test showed no evidence of a small fibre neuropathy either. However, serologic evaluation, performed to screen for potential peripheral neuropathy causes prior to our evaluation, showed a triclonal gammopathy of uncertain significance (IgG j, IgG k and IgA j). Congo red stain performed on an abdominal fat aspirate was positive for amyloid (Figure 1), raising the possibility of systemic amyloidosis. The patient had TTR sequencing which revealed no mutation. Upon questioning about insulin injections, known to cause focal amyloid deposits, the patient acknowledged using liraglutide 0.6mg subcutaneously once daily. Typing of the amyloid deposit by mass spectrometry-based proteomics (liquid chromatography with tandem mass spectrometry; LC-MS-MS) using previously published methods confirmed the presence of liraglutide-type amyloid deposit (Figure 1) [3]. Immunohistochemical studies were not performed because the specimen was a fat aspirate and hence, paraffin-embedded samples were not available. Liraglutide is an acylated glucagon-like peptide-1 analogue that is administered as a subcutaneous injection for the treatment of type 2 diabetes mellitus. To date, a single case of liraglutide-type amyloidosis has been reported [4]. Liraglutide should be considered as a potential amyloidogenic agent. Our case highlights the importance of