Hereditary lysozyme amyloidosis – phenotypic heterogeneity and the role of solid organ transplantation

Abstract

Abstract. Sattianayagam PT, Gibbs SDJ, Rowczenio D, Pinney JH, Wechalekar AD, Gilbertson JA, Hawkins PN, Lachmann HJ, Gillmore JD (University College London Medical School, London, UK). Hereditary lysozyme amyloidosis – phenotypic heterogeneity and the role of solid organ transplantation. J Intern Med 2012; 272: 36–44.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.

Amyloidosis of the gastrointestinal tract: a 13-year, single-center, referral experience

“…23 In keeping with prior reports, all of the patients with ALys amyloidosis in our series presented with symptomatic GI amyloidosis proven by biopsy. Their presentation was very similar to that described in another report; 7 however, in contrast to that study, none of our patients is known to have undergone either liver or renal transplantation, and all are still alive.…”

Understanding the dual nature of lysozyme: part villain – part hero : A Drosophila melanogaster model of lysozyme amyloidosis

“…Several mutations in the gene coding for human lysozyme are connected to non-neuropathic systemic amyloidosis; which is a hereditary disease where large amounts of lysozyme amyloid deposits are formed, ultimately leading to death (30,31). These deposits can be found in vital organs such as the upper gastrointestinal (GI) tract, throughout the colon and in the kidneys.…”

“…These deposits can be found in vital organs such as the upper gastrointestinal (GI) tract, throughout the colon and in the kidneys. The deposits cause organ failure, frequently through organ rupture (31,32). Table 1 (38) In one of the first reported cases of lysozyme amyloidosis (36), a 15-year old boy was presented, he had abdominal pain that progressively got worse; at age 13 he had got a diagnosis of amyloidosis.…”

Amyloidosis

“…15 However, in patients without a family history of amyloid disease, a hereditary type of amyloidosis may be present. 16 In patients with almost exclusive kidney disease, other types should be considered, such as fibrinogen a, 17 lysozyme, 18 apolipoprotein A I, apolipoprotein A II, apolipoprotein A IV, and the recently described leukocyte chemotactic factor-2. 19 In patients with almost exclusive cardiac or neuropathic disease, the apolipoprotein A I type should not be overlooked.…”