title: Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy.
abstract: Hereditary transthyretin amyloidosis (ATTR) is a genetically and clinically heterogeneous disease manifesting with predominant peripheral and autonomic neuropathy; cardiomyopathy, or both. ATTR V122I is the most common variant associated with non-neuropathic familial amyloid cardiomyopathy. We present an unusual case of V122I amyloidosis with features of amyloid neuropathy and myopathy, supported by histological confirmation in both sites and diffuse tracer uptake on (99m)Tc-3,3-Diphosphono-1,2-Propanodicarboxylic acid (DPD) scintigraphy throughout skeletal and cardiac muscle. A 64 year old Jamaican man presented with cardiac failure. Cardiac MR revealed infiltrative cardiomyopathy; abdominal fat aspirate confirmed the presence of amyloid, and he was homozygous for the V122I variant of transthyretin. He also described general weakness and EMG demonstrated myopathic features. Sural nerve and vastus lateralis biopsy showed TTR amyloid. The patient is being treated with diflunisal, an oral TTR stabilising agent. Symptomatic myopathy and neuropathy with confirmation of tissue amyloid deposition has not previously been described. Extracardiac amyloidosis has implications for diagnosis and treatment.
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK. Electronic address: Aisling.carr@uclh.nhs.uk.
authors.forename: A S
authors.initials: AS
authors.lastname: Carr
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK; University Hospital "Marqués de Valdecilla", Department of Neurology, Santander, Spain.
authors.forename: A L
authors.initials: AL
authors.lastname: Pelayo-Negro
authors.affiliation: Division of Neuropathology, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Jaunmuktane
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK; Division of Neuropathology, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: R S
authors.initials: RS
authors.lastname: Scalco
authors.affiliation: National Amyloidosis Centre, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
authors.forename: D
authors.initials: D
authors.lastname: Hutt
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: M R B
authors.initials: MR
authors.lastname: Evans
authors.affiliation: Division of Neuropathology, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Heally
authors.affiliation: Division of Neuropathology, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Brandner
authors.affiliation: Division of Neuropathology, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Holton
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK; Department of Clinical Neurophysiology, Norfolk and Norwich University Hospital, Norwich, UK.
authors.forename: J
authors.initials: J
authors.lastname: Blake
authors.affiliation: National Amyloidosis Centre, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Whelan
authors.affiliation: National Amyloidosis Centre, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Wechalekar
authors.affiliation: National Amyloidosis Centre, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Gillmore
authors.affiliation: National Amyloidosis Centre, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
authors.forename: P N
authors.initials: PN
authors.lastname: Hawkins
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital of Neurology and Neurosurgery, Queen Square, London, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Reilly
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D006331:Heart Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000175:diagnosis
keywords: Cardiomyopathy; Hereditary amyloidosis; Myopathy; Neuropathy; Transthyretin