Amyloid Neuropathy: Five Year Retrospective Case Review at a Tertiary Center.
Priya Devi Shanmugarajah, MBChB; Sajitha Chanaka Weerasinghe, MBBS; Agam Jung, MD
Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
Introduction Amyloidosis is a rare life-threatening multisystem disorder characterised by tissue deposition of insoluble fibril proteins with an incidence of 47:100000 in Europe. We describe two distinct cases of amyloid neuropathy from a five year retrospective case review.
Materials & Methods Thirty-two sural nerve biopsies were performed from 2011 to 2016 on patients with peripheral neuropathy and we describe two cases with biopsy proven amyloidosis.
Case 1 65-year-old man with lambda monoclonal gammopathy of undetermined significance (MGUS) presented with progressive sensory loss and lower limb weakness. He had multiple falls, urinary and faecal incontinence. Examination revealed postural hypotension, impaired pain sensation up to his knees, absent ankle jerks and bilateral foot drop.
Case 2 67-year-old man with bilateral carpal tunnel syndrome presented with weight loss, dysphagia, constipation, bilateral foot drop and numbness up to his waist. He constantly feels cold even in warm weather. There was no family history. Examination revealed postural hypotension, weak distal more than proximal lower limb muscle with symmetrical loss of pain sensation and globally attenuated reflexes.
Results In both cases, neurophysiology showed axonal sensory-motor polyneuropathy and sural nerve biopsy confirmed amyloid deposit on Congo red stain. SAP-scintigraphy revealed amyloid deposit in spleen and kidneys in case 1. He was diagnosed with systemic light-chain (AL) amyloidosis using immunofixation electrophoresis. He declined cyclophosphamide and stem cell transplant and was symptomatically managed. Case 2 had significant cardiac involvement of amyloidosis. Genetic testing confirmed transthyretin-T60A-variant mutation confirming Transthyretin (TTR)-related amyloidosis (ATTR). Symptom onset to diagnosis was five years for case 1 and eight years for case 2. Both patients died within ten years of symptom onset with multi-organ failure.
Conclusion Case 1 describes acquired primary AL amyloidosis caused by accumulation of immunoglobulin light chains in the setting of plasma cell dyscrasia in MGUS. Case 2 depicts autosomal dominant hereditary familial amyloid polyneuropathy (FAP). Met30TTR mutation is the most common of the 100 point mutations identified, with 52-77% of cases being sporadic. National Amyloidosis Centre reports cardiac involvement in nearly 100% of T60A-FAP patients with neuropathy. A study in a Mayo Clinic demonstrated a median time to diagnosis of 24 months (IQR, 3-384 months). Prompt treatment aims to delay disease progression by preventing amyloidogenesis. Chemotherapy and hematopoietic cell transplantation for AL amyloidosis and liver transplant for Met30TTR-FAP. High index of suspicion of amyloidosis is crucial when peripheral neuropathy and autonomic dysfunction is encountered, for early diagnosis and pertinent treatment.
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