Lysozyme amyloid related amyloidosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]
Synonyms and keywords:Lysozyme amyloidosis, ALys, Hereditory amyloidosis, autosomal dominant amyloidosis, Hereditary lysozyme amyloidosis, Familial amyloid nephropathy due to lysozyme variant, Familial renal amyloidosis due to lysozyme variant, Hereditary amyloid nephropathy due to lysozyme variant, Hereditary renal amyloidosis due to lysozyme variant
Overview
Lysozyme amyloid related amyloidosis is one of the subtypes of familial amyloidosis, it is associated with four mutations include, Ile56Thr, Asp67His, Trp64Arg, and Phe57Ile. It is an extremely rare disease and it commonly affects individuals in their third to fourth decades of life. Manifestation of the disease are based on which organs are involved, and include GI symptoms, renal impairment, sicca syndrome, lymphadenopathy, splenomegaly, and petechiae or purpura. The diagnosis of lysozyme amyloid related amyloidosis is based on the family history, histologic examination and amino acid sequencing. There is no treatment for lysozyme amyloid related amyloidosis; the mainstay of therapy is supportive care. Organ transplant could be done as palliative treatment.
Historical Perspective
- In 1639, Nicolaus Fontanus autopsied a young man who had ascites, jaundice, liver abscess, and splenomegaly and his report has been the first description of amyloidosis.[1]
- In 1854, Rudolph Virchow introduced the term "amyloid" as a macroscopic abnormality in some tissues.[2]
- In 1867, Weber reported the first case of amyloidosis associated with multiple myeloma.[1]
- In 1922, Bennhold introduced Congo Red staining of amyloid that remains the gold standard for diagnosis.[3]
- In 1959, Cohen and Calkins used ultrathin sections of amyloidotic tissues and assessed by electron microscopy, explained the presence of non-branching fibrils with indeterminate length and variable width.[2][1]
- In 1993, Pepys introduced that lysozyme form as an an amyloid fibril protein is a variant of hereditary systemic amyloidosis.[4]
Classification
Lysozyme amyloid related amyloidosis is one of the subtypes of familial amyloidosis. Familiar amyloidosis may be classified according to the type of mutant protein into 6 subtypes:[5][6][7]
- Transthyretin (TTR)
- Apolipoprotein AI
- Apolipoprotein AII
- Fibrinogen Aa
- Lysozyme
- Gelsolin
- Cystatin C
| Familial amyloidosis subtypes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Transthyretin (TTR) | Apolipoprotein AI | Gelsolin | Lysozyme | Cystatin C | Fibrinogen Aa-chain | Apolipoprotein AII | |||||||||||||||||||||||||||||||||||||||||||||||||||
Pathophysiology
- It is understood that amyloidosis is the result of deposition of Amyloid.[8]
- Amyloid is an abnormal insoluble extracellular protein which may cause organic dysfunction and a wide variety of clinical syndromes.
- These abnormal amyloids are derived from misfolding and aggregation of normally soluble proteins.
- Amyloid depositions also have glycosaminoglycans and serum amyloid P component (SAP) which alter the propensity for amyloid formation.[9][10][11]
- Amyloid deposition can disrupt tissue structure of involved organ and consequently leads to organ failure.[12]
Genetics
There are four genetic mutations which are associated with lysozyme amyloid related amyloidosis. include:[4]
- Ile56Thr
- Asp67His
- Trp64Arg
- Phe57Ile
Causes
Common cause of lysozyme amyloid related amyloidosis is genetic mutations.[13][5][6][14]
Lysozyme amyloid related amyloidosis must be differentiated from other types of familial amyloidosis and other diseases that mimic amyloidosis and may present as organ dysfunction, specifically, nephrotic syndrome leading to renal failure, cardiac failure and polyneuropathy.
For more information on the differential diagnosis of lysozyme amyloid related amyloidosis click here
Epidemiology and Demographics
- The incidence of amyloidosis is approximately 1.2 per 100,000 individuals per year worldwide.[15]
- The mortality rate of systemic amyloidosis is approximately 100 per 100,000 deaths in developed countries.[16]
- Lysozyme amyloid related amyloidosis commonly affects individuals in their third to fourth decades of life.[5]
- Hereditary amyloidosis subtypes include a substitution of an amino acid that is detected in approximately 4% of the african american population.[3]
- Men are more commonly affected by amyloidosis than women.[17]
Risk Factors
The most potent risk factor in the development of lysozyme amyloid related amyloidosis is positive familial history. Other risk factors include older age, male gender, and African-American race.[17][3][18]
Screening
There is insufficient evidence to recommend routine screening for lysozyme amyloid related amyloidosis.
Natural History, Complications, and Prognosis
- Important complication of lysozyme amyloid related amyloidosis is heavy bleeding caused by hepatic rupture and/or hemorrhagic lymph node rupture.[19]
Note: Because the risk of bleeding in this patients, liver biopsy should not be performed in suspected ones.[20]
Diagnosis
Diagnostic Study of Choice
- The diagnosis of lysozyme amyloid related amyloidosis is based on the family history, histologic examination and amino acid sequencing.[19]
History and Symptoms
- Common symptoms of lysozyme amyloid related amyloidosis include fatigue, weight loss and, edema.[21][22]
- Other symptoms of lysozyme amyloid related amyloidosis include sicca, diarrhea, nausea, abdominal discomfort, GI bleeding, worsening kidney function.[23][24][4][25]
Physical Examination
Physical examination of patients with lysozyme amyloid related amyloidosis is usually remarkable for renal impairment, petechiae, purpura, lymphadenopathy, and splenomegaly.[26][24][4][25][27][28]
Laboratory Findings
- Common tests that are abnormal in liver function tests including AST, ALT, total bilirubin, alkaline phosphatase, and albumin.[29][22][30]
- Common tests that are abnormal in renal function tests including serum creatinine, urinary protein, glomerular filtration rate, and albumin to creatinine ratio in the urine.
Electrocardiogram
Although, cardiac involvement is so rare in lysozyme amyloid related amyloidosis, electrocardiography may be done for cardiac analysis..
X-ray
There are no x-ray findings associated with lysozyme amyloid related amyloidosis.
Echocardiography or Ultrasound
Although, cardiac involvement is so rare in lysozyme amyloid related amyloidosis, echocardiography may be done for cardiac analysis.
CT scan
There are no CT scan findings associated with lysozyme amyloid related amyloidosis.
MRI
There are no MRI findings associated with lysozyme amyloid related amyloidosis.
Other Imaging Findings
Total body SAP component scintigraphy may be helpful in the diagnosis of lysozyme amyloid related amyloidosis. It can show lysozyme amyloid deposition and extension of it in the liver, spleen, kidney, adrenal glands, and bone marrow.[19]
Other Diagnostic Studies
- Tissue biopsy with Congo red stain is diagnostic for lysozyme amyloid related amyloidosis.[31][19]
- Biopsy of tissue may be taken from an affected organ like kidney, subcutaneous fat, digestive tract, or labial salivary glands.
- Immunohistochemistry using a polyclonal antibody against lysozyme is also used in diagnosis of the disease.
- Direct in vitro amino acid sequencing for typing of amyloid fibril proteins is the definite technique for diagnosis of lysozyme amyloid related amyloidosis.
Treatment
Medical Therapy
There is no treatment for lysozyme amyloid related amyloidosis; the mainstay of therapy is supportive care.[32]
Surgery
- Kidney transplant may be effective in patients with minor or absent extrarenal visceral involvement.[33][34]
- Liver transplant may be used as a palliative treatment.[35][36]
Primary Prevention
There are no established measures for the primary prevention of lysozyme amyloid related amyloidosis.
Secondary Prevention
Effective measures for the secondary prevention of lysozyme amyloid related amyloidosis include:[19]
References
- ↑ 1.0 1.1 1.2 Kyle RA (June 2011). "Amyloidosis: a brief history". Amyloid. 18 Suppl 1: 6–7. doi:10.3109/13506129.2011.574354001. PMID 21838413.
- ↑ 2.0 2.1 Sipe JD, Cohen AS (June 2000). "Review: history of the amyloid fibril". J. Struct. Biol. 130 (2–3): 88–98. doi:10.1006/jsbi.2000.4221. PMID 10940217.
- ↑ 3.0 3.1 3.2 Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
- ↑ 4.0 4.1 4.2 4.3 Pepys, M. B.; Hawkins, P. N.; Booth, D. R.; Vigushin, D. M.; Tennent, G. A.; Soutar, A. K.; Totty, N.; Nguyen, O.; Blake, C. C. F.; Terry, C. J.; Feest, T. G.; Zalin, A. M.; Hsuan, J. J. (1993). "Human lysozyme gene mutations cause hereditary systemic amyloidosis". Nature. 362 (6420): 553–557. doi:10.1038/362553a0. ISSN 0028-0836.
- ↑ 5.0 5.1 5.2 Benson, Merrill D (2003). "The hereditary amyloidoses". Best Practice & Research Clinical Rheumatology. 17 (6): 909–927. doi:10.1016/j.berh.2003.09.001. ISSN 1521-6942.
- ↑ 6.0 6.1 Benson, Merrill D (2003). "The hereditary amyloidoses". Best Practice & Research Clinical Rheumatology. 17 (6): 909–927. doi:10.1016/j.berh.2003.09.001. ISSN 1521-6942.
- ↑ Scriver, Charles (2001). The metabolic & molecular bases of inherited disease. New York: McGraw-Hill. ISBN 978-0079130358.
- ↑ Wechalekar AD, Gillmore JD, Hawkins PN (June 2016). "Systemic amyloidosis". Lancet. 387 (10038): 2641–2654. doi:10.1016/S0140-6736(15)01274-X. PMID 26719234.
- ↑ Pepys MB, Rademacher TW, Amatayakul-Chantler S, Williams P, Noble GE, Hutchinson WL, Hawkins PN, Nelson SR, Gallimore JR, Herbert J (June 1994). "Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure". Proc. Natl. Acad. Sci. U.S.A. 91 (12): 5602–6. doi:10.1073/pnas.91.12.5602. PMC 44044. PMID 8202534.
- ↑ Tan SY, Pepys MB (November 1994). "Amyloidosis". Histopathology. 25 (5): 403–14. doi:10.1111/j.1365-2559.1994.tb00001.x. PMID 7868080.
- ↑ Botto M, Hawkins PN, Bickerstaff MC, Herbert J, Bygrave AE, McBride A, Hutchinson WL, Tennent GA, Walport MJ, Pepys MB (August 1997). "Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene". Nat. Med. 3 (8): 855–9. doi:10.1038/nm0897-855. PMID 9256275.
- ↑ Wechalekar AD, Gillmore JD, Hawkins PN (June 2016). "Systemic amyloidosis". Lancet. 387 (10038): 2641–2654. doi:10.1016/S0140-6736(15)01274-X. PMID 26719234.
- ↑ Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA, Soutar AK, Totty N, Nguyen O, Blake CC, Terry CJ (April 1993). "Human lysozyme gene mutations cause hereditary systemic amyloidosis". Nature. 362 (6420): 553–7. doi:10.1038/362553a0. PMID 8464497.
- ↑ Scriver, Charles (2001). The metabolic & molecular bases of inherited disease. New York: McGraw-Hill. ISBN 978-0079130358.
- ↑ Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
- ↑ Pepys MB (2006). "Amyloidosis". Annu. Rev. Med. 57: 223–41. doi:10.1146/annurev.med.57.121304.131243. PMID 16409147.
- ↑ 17.0 17.1 Shin YM (March 2011). "Hepatic amyloidosis". Korean J Hepatol. 17 (1): 80–3. doi:10.3350/kjhep.2011.17.1.80. PMC 3304630. PMID 21494083.
- ↑ Shin YM (March 2011). "Hepatic amyloidosis". Korean J Hepatol. 17 (1): 80–3. doi:10.3350/kjhep.2011.17.1.80. PMC 3304630. PMID 21494083.
- ↑ 19.0 19.1 19.2 19.3 19.4 Granel, Brigitte; Valleix, Sophie; Serratrice, Jacques; Chérin, Patrick; Texeira, Antonio; Disdier, Patrick; Weiller, Pierre-Jean; Grateau, Gilles (2006). "Lysozyme Amyloidosis". Medicine. 85 (1): 66–73. doi:10.1097/01.md.0000200467.51816.6d. ISSN 0025-7974.
- ↑ Harrison, R F; Hawkins, P N; Roche, W R; MacMahon, R F; Hubscher, S G; Buckels, J A (1996). "'Fragile' liver and massive hepatic haemorrhage due to hereditary amyloidosis". Gut. 38 (1): 151–152. doi:10.1136/gut.38.1.151. ISSN 0017-5749.
- ↑ Lim AY, Lee JH, Jung KS, Gwag HB, Kim DH, Kim SJ, Lee GY, Kim JS, Kim HJ, Lee SY, Lee JE, Jeon ES, Kim K (July 2015). "Clinical features and outcomes of systemic amyloidosis with gastrointestinal involvement: a single-center experience". Korean J. Intern. Med. 30 (4): 496–505. doi:10.3904/kjim.2015.30.4.496. PMC 4497337. PMID 26161016.
- ↑ 22.0 22.1 Baker KR, Rice L (2012). "The amyloidoses: clinical features, diagnosis and treatment". Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
- ↑ J. G. Lanham, M. L. Meltzer, F. C. De Beer, G. R. Hughes & M. B. Pepys (1982). "Familial amyloidosis of Ostertag". The Quarterly journal of medicine. 51 (201): 25–32. PMID 7111672.
- ↑ 24.0 24.1 Gillmore, Julian D.; Booth, David R.; Madhoo, S.; Pepys, Mark B.; Hawkins, Philip N. (1999). "Hereditary renal amyloidosis associated with variant lysozyme in a large English family". Nephrology Dialysis Transplantation. 14 (11): 2639–2644. doi:10.1093/ndt/14.11.2639. ISSN 1460-2385.
- ↑ 25.0 25.1 Yood, Robert A. (1983). "Bleeding Manifestations in 100 Patients With Amyloidosis". JAMA: The Journal of the American Medical Association. 249 (10): 1322. doi:10.1001/jama.1983.03330340064034. ISSN 0098-7484.
- ↑ J. G. Lanham, M. L. Meltzer, F. C. De Beer, G. R. Hughes & M. B. Pepys (1982). "Familial amyloidosis of Ostertag". The Quarterly journal of medicine. 51 (201): 25–32. PMID 7111672.
- ↑ Segalov, Eva; Gibson, John; Joshua, Douglas E.; Kronenberg, Harry (2009). "Primary Amyloidosis Co-Presenting with Cervical and Massive Intra-Abdominal Lymphadenopathy". Leukemia & Lymphoma. 19 (5–6): 519–520. doi:10.3109/10428199509112215. ISSN 1042-8194.
- ↑ "Familial Nephropathic Non-neuropathic Amyloidosis: Clinical Features, Immunohistochemistry and Chemistry". QJM: An International Journal of Medicine. 1991. doi:10.1093/oxfordjournals.qjmed.a068643. ISSN 1460-2393.
- ↑ Merlini G, Seldin DC, Gertz MA (May 2011). "Amyloidosis: pathogenesis and new therapeutic options". J. Clin. Oncol. 29 (14): 1924–33. doi:10.1200/JCO.2010.32.2271. PMC 3138545. PMID 21483018.
- ↑ Real de Asúa D, Costa R, Galván JM, Filigheddu MT, Trujillo D, Cadiñanos J (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clin Epidemiol. 6: 369–77. doi:10.2147/CLEP.S39981. PMC 4218891. PMID 25378951.
- ↑ Benson MD, Yazaki M, Magy N (December 2002). "Laboratory assessment of transthyretin amyloidosis". Clin. Chem. Lab. Med. 40 (12): 1262–5. doi:10.1515/CCLM.2002.218. PMID 12553428.
- ↑ Pleyer, Christopher; Flesche, Jan; Saeed, Fahad (2015). "Lysozyme amyloidosis – a case report and review of the literature". Clinical Nephrology Case Studies. doi:10.5414/CNCS108538. ISSN 2196-5293.
- ↑ Yazaki, Masahide; Farrell, Sandra A.; Benson, Merrill D. (2003). "A novel lysozyme mutation Phe57Ile associated with hereditary renal amyloidosis". Kidney International. 63 (5): 1652–1657. doi:10.1046/j.1523-1755.2003.00904.x. ISSN 0085-2538.
- ↑ Valleix, Sophie; Drunat, Séverine; Philit, Jean-Baptiste; Adoue, Daniel; Piette, Jean-Charles; Droz, Dominique; MacGregor, Brigitte; Canet, Denis; Delpech, Marc; Grateau, Gilles (2002). "Hereditary renal amyloidosis caused by a new variant lysozyme W64R in a French family". Kidney International. 61 (3): 907–912. doi:10.1046/j.1523-1755.2002.00205.x. ISSN 0085-2538.
- ↑ Sattianayagam, P. T.; Gibbs, S. D. J.; Rowczenio, D.; Pinney, J. H.; Wechalekar, A. D.; Gilbertson, J. A.; Hawkins, P. N.; Lachmann, H. J.; Gillmore, J. D. (2012). "Hereditary lysozyme amyloidosis - phenotypic heterogeneity and the role of solid organ transplantation". Journal of Internal Medicine. 272 (1): 36–44. doi:10.1111/j.1365-2796.2011.02470.x. ISSN 0954-6820.
- ↑ Loss, Martin; Ng, Wa S.; Karim, Rooshdiya Z.; Strasser, Simone I.; Koorey, David J.; Gallagher, Peter J.; Verran, Deborah J.; McCaughan, Geoffrey W. (2006). "Hereditary lysozyme amyloidosis: Spontaneous hepatic rupture (15 years apart) in mother and daughter. role of emergency liver transplantation". Liver Transplantation. 12 (7): 1152–1155. doi:10.1002/lt.20803. ISSN 1527-6465.