LAUSR

Hereditary amyloidosis with autosomal-dominant mutations in the transthyretin-gene (TTR) represents a severe multisystem disorder. Treatment options are now available for TTR familial amyloid polyneuropathy (TTR-FAP): patisiran [1], inotersen [2], tafamidis [3] and orthotopic liver transplantation (OLT). It is known that TTR-cardiomyopathy and neurologic symptoms progress in many transplant recipients. This disease progression after transplantation occurs mainly in patients who are late stage with (p.Val50Met) or have a mutation other than (p.Val50Met) [4]. In these cases, the management strategy is unclear. One small study showed stable neuropathy scores during 12-month treatment with Inotersen after OLT [5]. Tafamidis stabilized TTR-FAP symptoms in one woman for 18 months [6]. Patisiran stabilizes neurological symptoms for 12 months after OLT [7]. No data are available, so far, on how to escalate amyloidosis therapy in case of disease progression after OLT during ongoing therapy with one of the approved agents. We herewith present a case of a young man who had severe TTR-FAP progression after OLT. Tafamidis therapy did not stop disease progression, but the patient showed clinical improvement of the TTR-FAP after switch to patisiran. A now 44-year-old man was diagnosed with TTR-FAP in 2012 caused by a rare TTR mutation (p.Glu54Gly) at the age of 36 years. The diagnosis occurred early because of his positive family history. Pre-existing conditions included chronic hepatitis B and D. At diagnosis, he reported autonomic disturbance causing gastrointestinal symptoms (constipation and diarrhoea) and noticed signs of small-fibre involvement (inability to detect temperatures) for approximately 1 year. Physical examination revealed slightly reduced muscle strength in the extensor muscles of the toes, distal hypesthesia in both feet, pallhypesthesia with 4/8 at the first metatarsophalangeal joints and absent achilles tendon reflexes. Nerve conduction studies (NCS) detected absent sensory responses in the lower limbs and decreased compound muscle action potential (CMAP) of the peroneal nerves. The mNIS + 7score was 31 points [1]. Echocardiography revealed an inhomogeneous echotexture of the myocardium, a slightly reduced systolic function with normal radial and impaired longitudinal function and increased septal thickness (16 mm). A cardiac MRI performed in 2013 confirmed reduced systolic function (ejection fraction 52%) and septal hypertrophy. Further, it showed a diffuse late gadolinium enhancement with a non-ischaemic pattern as described in cardiac involvement in amyloidosis. The patient was diagnosed with NYHA stadium I-II and sensorimotor axonal polyneuropathy (Coutinho stage 1). Oral therapy with tafamidis was started. A living split-liver transplantation was performed 2013 without any complications. After OLT, tafamidis medication was discontinued. However, the symptoms of the polyneuropathy slowly increased. In spring 2018, tafamidis medication was re-established. By this time, the patient’s complaints comprised of weakness in the legs, sensory loss in the feet, paraesthesia in the hands and postprandial hypotonia indicating autonomic neuropathy. Physical examination revealed paresis of the small hand muscles (MRC 4/5), the extensor muscles of the feet (MRC 2/5), areflexia at the lower extremities and pallanaesthesia at the first metatarsophalangeal joints. NCS detected absent sensory responses in all limbs and absent CMAP of the peroneal and significantly reduced CMAP of the tibial nerves (mNIS-7 score: 149.5). Echocardiography showed rather constant hypertrophy of the * Catherine Bulinski [email protected]