Hereditary renal amyloidosis associated with variant lysozyme in a large English family

Gillmore, Julian D.; Booth, David R.; Madhoo, S; Pepys, Mark B.; Hawkins, Philip N.

doi:10.1093/ndt/14.11.2639

Cited by 73 publications

(48 citation statements)

References 15 publications

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“…Age at presentation and rate of renal progression varied widely, even amongst patients from the same family who carried the same mutation, evident from Family 4 in this series and consistent with previous reports [4,5,25]. Despite a large total body amyloid burden and a complete lack of available therapy to halt amyloid accumulation in ALys, outcomes amongst three RTx recipients were excellent with functioning renal allografts and no recurrence of amyloid 0.8, 1.8 and 6.6 years after RTx.…”

Section: Discussionsupporting

confidence: 91%

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

Sattianayagam

Gibbs

Rowczenio

et al. 2011

Journal of Internal Medicine

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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.

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Section: Discussionsupporting

confidence: 91%

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

Sattianayagam

Gibbs

Rowczenio

et al. 2011

Journal of Internal Medicine

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“…27,28 The patient with the Ala175Pro variant of apolipoprotein A-I, a newly identified variant, had hoarseness due to laryngeal amyloid deposits, a feature that commonly occurs in localized AL amyloidosis and that has also been reported in patients with mutations that disrupt this region of the apolipoprotein A-I molecule. 29,30 AL amyloidosis often responds to chemotherapy that suppresses the underlying clonal plasma-cell disorder, 2-5 but chemotherapy has no role in the treatment of hereditary amyloidosis and is dangerous.…”

Section: Discussionmentioning

confidence: 99%

Misdiagnosis of Hereditary Amyloidosis as AL (Primary) Amyloidosis

et al. 2002

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“…Hereditary systemic amyloidosis with renal involvement may result from deposits of apolipoprotein A-I, apolipoprotein A-II, lysozyme [38], and fibrinogen, all of which produce clinical syndromes indistinguishable from AL [39]. Hepatic amyloidosis occurs in apolipoprotein A-I, lysozyme, immunoglobulin light chain, and AA types [40,41].…”

Section: How Is the Amyloidosis Characterized As Al Type?mentioning

confidence: 99%

Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

et al. 2005

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Hereditary renal amyloidosis associated with variant lysozyme in a large English family

Cited by 73 publications

References 15 publications

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

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

Misdiagnosis of Hereditary Amyloidosis as AL (Primary) Amyloidosis

Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

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