Diagnosis of familial amyloidotic polyneuropathy by bone marrow biopsy

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A 58-year-old man presented with dysphagia, progressive paraesthesia and weakness of the legs. A nerve conduction test showed generalized axonal sensorimotor polyneuropathy. Serum immunoglobulin levels were normal, and no paraprotein was demonstrated. Peripheral blood counts were normal. Bone marrow examination showed active haematopoiesis without any increase in plasma cells. A small vessel in the periosteum, however, showed deposits of eosinophilic material (top) that exhibited apple-green birefringence on a Congo Red stain. An immunohistochemical study using an antibody to amyloid P protein was positive. Neurological involvement was confirmed by a sural nerve biopsy, which showed axonal degeneration and amyloid deposition. Electron microscopy showed focal deposition of non-branching fibrils measuring 7·4–10·4 nm in the wall of a small vessel (bottom).

The family history revealed that the patient's elder brother had had cardiomyopathy for many years, although he did not have neurological symptoms. Molecular testing showed that the patient was heterozygous for a disease-causing mutation of Ala97Ser in exon 4 of the transthyretin gene (TTR). A family study confirmed that his elder brother also carried the same mutation, and a diagnosis of familial amyloidotic polyneuropathy type 1 was made. This condition polyneuropathy type 1, caused by TTR mutations, is a rare autosomal dominant disease characterized by late onset progressive polyneuropathy, autonomic dysfunction and cardiomyopathy. The present case highlights the importance of examining tissues outside the bone marrow cavity when interpreting trephine biopsy sections.

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