muramidase and Rupture--Spontaneous

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.. Retrospective evaluation of patients with ALys.. UK National Amyloidosis Centre.. All 16 patients with ALys followed at the centre.. 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.. 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.

Topics: Adult; Aged; Amyloidosis, Familial; Child; Female; Gastrointestinal Diseases; Humans; Kidney Failure, Chronic; Kidney Transplantation; Liver Diseases; Liver Transplantation; Lymphatic Diseases; Male; Middle Aged; Muramidase; Mutation; Peptic Ulcer Hemorrhage; Phenotype; Purpura; Radionuclide Imaging; Retrospective Studies; Rupture, Spontaneous; Serum Amyloid P-Component; Sjogren's Syndrome; Survival Analysis; United Kingdom

Hepatic rupture is a rare condition, and treatment options are very limited. We report a case of hepatic rupture secondary to hereditary lysozyme amyloidosis that was successfully treated by liver transplantation. The mother of this patient had presented in an identical fashion 15 years earlier in the pretransplant era and died very rapidly.

Topics: Adult; Amyloidosis, Familial; Emergency Medical Services; Female; Humans; Liver Transplantation; Middle Aged; Mothers; Muramidase; Nuclear Family; Rupture, Spontaneous; Time Factors; Treatment Outcome

Pathological examination in the spleen of an 81-year old female with hemoperitoneum, hypovolemic shock, anemia, thrombocytopenia and hyperglicemia revealed the presence of an angiosarcoma. On histological examination, characteristically the neoplasm was formed by vascular lumina and cystic spaces into which papillary fronds projected and solid nests. Neoplastic cells had scant cytoplasm, hyperchromatic, oval or reniform nuclei, with prominent nucleoli. The necrosis was evident and mitoses were frequent. Immunohistochemical analysis revealed positivity for endothelial (CD31, CD34) and histiocytic markers (CD68 and lysozyme) and negativity for CD21. Ultrastructural examination also disclosed a biphasic differentiation, showing the presence of organelles associated with histiocytic and endothelial differentiation. These findings suggest that this lesion can be considered a conventional splenic angiosarcoma with focal histocytic differentiation.

Topics: Aged, 80 and over; Antigens, CD; Biomarkers, Tumor; Cell Nucleus; Fatal Outcome; Female; Hemangiosarcoma; Humans; Lysosomes; Muramidase; Necrosis; Rupture, Spontaneous; Splenic Neoplasms; Splenic Rupture