Abstract
Background Transthyretin amyloidosis, also known as familial amyloidotic polyneuropathy, is an autosomal dominant disorder that results from a mutation in the gene encoding plasma transthyretin (TTR). Distinct clinical presentations of the disease have been related so far to different point mutations, polyneuropathy being the predominant clinical feature in the majority of cases. Nevertheless, misdiagnosis of familial forms of amyloidosis is still common.
Materials and methods A 71‐year‐old man was admitted to our hospital for heart failure. He had been previously diagnosed of AL amyloidosis with predominant polyneuropathic, cardiac and laryngeal involvement on the basis of clinical data and amyloid deposition in tissue specimens. During admission, suspicion of transthyretin amyloidosis was raised due to the absence of renal involvement, monoclonal protein and plasma cell dyscrasia. Complete clinical evaluation and sequence analysis of the TTR gene of the patient and his family were performed.
Results Gene sequence analysis revealed a rare A‐to‐T transition in exon 2 resulting in the substitution of aspartic acid by valine at position 38 (D38V) in the index case and in two other members of the family. Clinical study of the kindred showed a predominant late‐onset heart involvement with variable polyneuropathy.
Conclusions Here we report a large pedigree from Spain with three members affected by a severe late‐onset form of amyloidosis due to a rare D38V TTR mutation. The variations on the natural history of this form of amyloidosis may have important consequences on genetic counselling, follow‐up, and therapeutic approaches for these patients.