Familial amyloid polyneuropathy associated with the novel transthyretin variant Arg34Gly.

We report a 57-year-old man with pathognomonic bilateral vitreo-lenticular amyloid opacities (pseudopodia lentis) in whom a novel transthyretin (TTR) mutation was identified. The patient presented due to bilateral floaters. The vitreous cavities of both eyes showed course, fibrilar opacities attached to the posterior lens surface with pseudopodia. There was a history of bilateral carpal tunnel syndrome. Nerve conduction studies showed upper and lower limb axonal polyneuropathy. Magnetic resonance imaging of the brain and spinal cord, renal and cardiac function were normal. Vitreous and conjunctival biopsies confirmed the diagnosis of TTR-related amyloidosis. Genetic analysis of exon 2 of the TTR gene revealed that the patient was heterozygous for a single nucleotide substitution c.160 A>G, resulting in replacement of arginine with glycine at position 34 of the mature protein (Arg34Gly). Five years later the patient developed increasing sensory and motor neuropathy of both lower limbs, and neovascular glaucoma in one eye. We hypothesize that the reason for his neovascular glaucoma was retinal ischaemia secondary to amyloid retinal vasculopathy.

Vogt-Koyanagi-Harada disease, diabetes mellitus, and psoriasis in a child.

PURPOSE: To report a case of a child with near-simultaneous onset of Vogt Koyanagi Harada disease (VKH) and insulin-dependent diabetes mellitus (IDDM). DESIGN: Interventional case report. METHODS: An 11-year-old child with known psoriasis presented with headache and bilateral granulomatous panuveitis. Nine weeks later, he presented with diabetic ketoacidosis and IDDM. Diffuse choroidal depigmentation followed within months. HLA was positive for DRB1*0405. Despite aggressive local and systemic therapy, the ocular disease was complicated by bilateral cataracts, angle closure glaucoma, and choroidal neovascularization. RESULTS: The patient is currently pseudophakic in one eye and aphakic in the other, with best-corrected visual acuity of 6/24 and 6/5, respectively. CONCLUSIONS: VKH may present in children with panuveitis in the setting of other autoimmune disorders. Treating such patients is complicated by the need to minimize systemic corticosteroid use. A combination of local therapy and systemic steroid-sparing agents should be the mainstay of treatment.

Thioflavin T fluorescence in human serum: correlations with vascular health and cardiovascular risk factors.

OBJECTIVES: Amyloid fibrils and amyloid-like structures are implicated in atherosclerosis via macrophage activation and inflammation. A common property of amyloid-like structures is their ability to induce thioflavin T (ThT) fluorescence. We measured ThT fluorescence in serum and related these levels to traditional cardiovascular risk factors and non-invasive measures of vascular dysfunction (elasticity). In addition, chemically modified serum components that contribute to serum ThT fluorescence were explored and identified. DESIGN, METHODS, AND RESULTS: Sera from 105 people, including 35 healthy subjects, and 70 high cardiovascular risk patients (36 with rheumatoid arthritis and 34 with systemic lupus erythrematosus) showed an 8.75-fold variation in induced ThT fluorescence. Although mean (+/-SD) ThT fluorescence did not differ significantly between groups (controls 0.97+/-0.26, RA 1.12+/-0.45, and SLE 0.74+/-0.23), the combined data set showed significant inverse correlation (p=0.046) between ThT fluorescence tertiles and small artery elasticity. Correlation was also found between ThT fluorescence tertiles and LDL-cholesterol, total-cholesterol, and C-reactive protein. Floatation fractionation of apoB containing lipoproteins showed that ThT reactivity in this fraction correlated with both serum oxidised-LDL and LDL-cholesterol levels. However, approximately 94% of ThT reactivity in serum was associated with the non-apoB containing serum fraction, with the majority of ThT fluorescence associated with albumin. Incubation of purified albumin with glucose or with methylglyoxal induced ThT fluorescence, suggesting that glycated or chemical adducts of albumin contribute to the variation in ThT fluorescence of human serum. CONCLUSIONS: We propose that the detection of these adducts in serum using ThT fluorescence measurements may provide a marker for chemically modified protein structures that could assist the assessment of cardiovascular disease risk.