OBJECTIVES: Lysozyme amyloidosis (ALys) is a form of hereditary systemic non-neuropathic amyloidosis, which is inherited in an autosomal dominant fashion. Lysozyme, which is the amyloidogenic precursor protein in ALys, is a ubiquitous bacteriolytic enzyme synthesized by hepatocytes, polymorphs and macrophages. The aim of this study is to describe the phenotype and outcome of patients with ALys including the role of solid organ transplantation. DESIGN: Retrospective evaluation of patients with ALys. SETTING: UK National Amyloidosis Centre. PATIENTS: All 16 patients with ALys followed at the centre. RESULTS: A family history of amyloidosis was present in every affected individual. Although the phenotype was broadly similar amongst those from the same kindred, there were marked phenotypic differences between kindreds who possessed the same amyloidogenic mutation. Symptomatic gastrointestinal (GI) amyloid was prevalent, and macroscopically visible amyloidotic lesions were present in nine of 10 patients who underwent GI endoscopy. All symptomatic ALys individuals had hepatic amyloid. Four patients received orthotopic liver transplants (OLT), three for spontaneous hepatic rupture and one case, who had extensive hepatic amyloid and a strong family history of hepatic rupture, pre-emptively. All of the liver grafts were functioning at censor 1.7, 5.8, 9.0 and 11.0 years after OLT. Five patients had progressive amyloidotic renal dysfunction culminating in end-stage renal failure, three of whom underwent renal transplantation (RTx). There was no evidence of renal allograft dysfunction at censor 6.6, 1.8 and 0.8 years after RTx. CONCLUSIONS: Lysozyme amyloidosis is a disease of the GI tract, liver and kidneys, which has a slow natural history. There was a clear family history in all cases within this cohort, demonstrating a high clinical penetrance in the presence of an amyloidogenic lysozyme mutation. There is currently no amyloid-specific therapy for the condition which is managed symptomatically. OLT and RTx appear to be successful treatments for patients with liver rupture or end-stage renal disease, respectively, with excellent outcomes in terms of medium-term graft function and patient survival.
OBJECTIVES:Lysozymeamyloidosis (ALys) is a form of hereditary systemic non-neuropathic amyloidosis, which is inherited in an autosomal dominant fashion. Lysozyme, which is the amyloidogenic precursor protein in ALys, is a ubiquitous bacteriolytic enzyme synthesized by hepatocytes, polymorphs and macrophages. The aim of this study is to describe the phenotype and outcome of patients with ALys including the role of solid organ transplantation. DESIGN: Retrospective evaluation of patients with ALys. SETTING: UK National Amyloidosis Centre. PATIENTS: All 16 patients with ALys followed at the centre. RESULTS: A family history of amyloidosis was present in every affected individual. Although the phenotype was broadly similar amongst those from the same kindred, there were marked phenotypic differences between kindreds who possessed the same amyloidogenic mutation. Symptomatic gastrointestinal (GI) amyloid was prevalent, and macroscopically visible amyloidotic lesions were present in nine of 10 patients who underwent GI endoscopy. All symptomatic ALys individuals had hepatic amyloid. Four patients received orthotopic liver transplants (OLT), three for spontaneous hepatic rupture and one case, who had extensive hepatic amyloid and a strong family history of hepatic rupture, pre-emptively. All of the liver grafts were functioning at censor 1.7, 5.8, 9.0 and 11.0 years after OLT. Five patients had progressive amyloidotic renal dysfunction culminating in end-stage renal failure, three of whom underwent renal transplantation (RTx). There was no evidence of renal allograft dysfunction at censor 6.6, 1.8 and 0.8 years after RTx. CONCLUSIONS:Lysozymeamyloidosis is a disease of the GI tract, liver and kidneys, which has a slow natural history. There was a clear family history in all cases within this cohort, demonstrating a high clinical penetrance in the presence of an amyloidogenic lysozyme mutation. There is currently no amyloid-specific therapy for the condition which is managed symptomatically. OLT and RTx appear to be successful treatments for patients with liver rupture or end-stage renal disease, respectively, with excellent outcomes in terms of medium-term graft function and patient survival.
Authors: Samih H Nasr; Surendra Dasari; John R Mills; Jason D Theis; Michael T Zimmermann; Rafael Fonseca; Julie A Vrana; Steven J Lester; Brooke M McLaughlin; Robert Gillespie; W Edward Highsmith; John J Lee; Angela Dispenzieri; Paul J Kurtin Journal: J Am Soc Nephrol Date: 2017-01-03 Impact factor: 10.121
Authors: Andrew J Cowan; Martha Skinner; David C Seldin; John L Berk; David R Lichtenstein; Carl J O'Hara; Gheorghe Doros; Vaishali Sanchorawala Journal: Haematologica Date: 2012-06-24 Impact factor: 9.941
Authors: Samih H Nasr; Surendra Dasari; Linda Hasadsri; Jason D Theis; Julie A Vrana; Morie A Gertz; Prasuna Muppa; Michael T Zimmermann; Karen L Grogg; Angela Dispenzieri; Sanjeev Sethi; W Edward Highsmith; Giampaolo Merlini; Nelson Leung; Paul J Kurtin Journal: J Am Soc Nephrol Date: 2016-06-13 Impact factor: 10.121
Authors: Tatiana Prokaeva; Harun Akar; Brian Spencer; Andrea Havasi; Haili Cui; Carl J O'Hara; Olga Gursky; John Leszyk; Martin Steffen; Sabrina Browning; Allison Rosenberg; Lawreen H Connors Journal: Kidney Int Rep Date: 2017-07-29
Authors: Olga V Stepanenko; Maksim I Sulatsky; Ekaterina V Mikhailova; Olesya V Stepanenko; Irina M Kuznetsova; Konstantin K Turoverov; Anna I Sulatskaya Journal: Int J Mol Sci Date: 2021-05-02 Impact factor: 5.923