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Amyloidosis, hereditary systemic 5(AMYLD5)

MedGen UID:
1859086
Concept ID:
C5935572
Disease or Syndrome
Synonyms: AMYLD5; AMYLOIDOSIS, HEREDITARY SYSTEMIC 5
 
Gene (location): LYZ (12q15)
 
Monarch Initiative: MONDO:0971009
OMIM®: 620658

Definition

Hereditary systemic amyloidosis-5 (AMYLD5) is a rare amyloidosis that can affect the viscera, with severe involvement when located in the kidneys and liver. Renal dysfunction of varying severity may be the predominant manifestation. Massive hepatic hemorrhage constitutes the other severe visceral involvement. Dermatologic manifestations are rare (summary by Granel et al., 2005). The various forms of hereditary systemic amyloidosis that do not have peripheral neuropathy as part of the clinical syndrome had been referred to as 'Ostertag type' (Benson, 2005). For a discussion of genetic heterogeneity of hereditary systemic amyloidosis, see AMYLD1 (105210). [from OMIM]

Clinical features

From HPO
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Renal amyloidosis
MedGen UID:
120633
Concept ID:
C0268382
Disease or Syndrome
A form of amyloidosis that affects the kidney. On hematoxylin and eosin stain, amyloid is identified as extracellular amorphous material that is lightly eosinophilic. These deposits often stain weakly for periodic acid Schiff (PAS), demonstrate a blue-to-gray hue on the trichrome stain and are typically negative on the Jones methenamine silver (JMS) stain. These tinctorial properties contrast with the histologic appearance of collagen, a major component of basement membranes, mesangial matrix and areas of sclerosis, which demonstrates strong positivity for PAS and JMS (See Figure 1 of PMID:25852856).
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Hepatic amyloidosis
MedGen UID:
75642
Concept ID:
C0267839
Disease or Syndrome
A form of amyloidosis that affects the liver.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Keratoconjunctivitis sicca
MedGen UID:
9620
Concept ID:
C0022575
Disease or Syndrome
Dryness of the eye related to deficiency of the tear film components (aqueous, mucin, or lipid), lid surface abnormalities, or epithelial abnormalities. Keratoconjunctivitis sicca often results in a scratchy or sandy sensation (foreign body sensation) in the eyes, and may also be associated with itching, inability to produce tears, photosensitivity, redness, pain, and difficulty in moving the eyelids.
Amyloidosis
MedGen UID:
272
Concept ID:
C0002726
Disease or Syndrome
The presence of amyloid deposition in one or more tissues. Amyloidosis may be defined as the extracellular deposition of amyloid in one or more sites of the body.
Conjunctival amyloidosis
MedGen UID:
75676
Concept ID:
C0268402
Disease or Syndrome
A form of amyloidosis that affects the conjunctiva.
Petechiae
MedGen UID:
10680
Concept ID:
C0031256
Disease or Syndrome
Petechiae are pinpoint-sized reddish/purple spots, resembling a rash, that appear just under the skin or a mucous membrane when capillaries have ruptured and some superficial bleeding into the skin has happened. This term refers to an abnormally increased susceptibility to developing petechiae.

Professional guidelines

PubMed

Nakov R, Suhr OB, Ianiro G, Kupcinskas J, Segal JP, Dumitrascu DL, Heinrich H, Mikolasevic I, Stojkovic-Lalosevic M, Barbov I, Sarafov S, Tournev I, Nakov V, Wixner J
Eur J Gastroenterol Hepatol 2021 May 1;33(5):613-622. doi: 10.1097/MEG.0000000000002030. PMID: 33394808
Weidner T, Illing T, Elsner P
Am J Clin Dermatol 2017 Oct;18(5):629-642. doi: 10.1007/s40257-017-0278-9. PMID: 28342017
Al Yahya RS
Lasers Med Sci 2016 Jul;31(5):1027-35. Epub 2016 Mar 16 doi: 10.1007/s10103-016-1917-8. PMID: 26984345

Recent clinical studies

Etiology

Goldis R, Kaplan B, Kukuy OL, Arad M, Magen H, Shavit-Stein E, Dori A, Livneh A
Int J Mol Sci 2023 Feb 28;24(5) doi: 10.3390/ijms24054655. PMID: 36902083Free PMC Article
Solís Marquínez MN, García Fernández E, Morís de la Tassa J
Reumatol Clin (Engl Ed) 2019 Sep-Oct;15(5):e39-e40. Epub 2017 Jun 2 doi: 10.1016/j.reuma.2017.04.008. PMID: 28583784
Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Planté-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceição I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T
N Engl J Med 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793. PMID: 29972757
Weidner T, Illing T, Elsner P
Am J Clin Dermatol 2017 Oct;18(5):629-642. doi: 10.1007/s40257-017-0278-9. PMID: 28342017
González-López E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C, Bornstein B, Salas C, Lara-Pezzi E, Alonso-Pulpon L, Garcia-Pavia P
Eur Heart J 2015 Oct 7;36(38):2585-94. Epub 2015 Jul 28 doi: 10.1093/eurheartj/ehv338. PMID: 26224076

Diagnosis

Goldis R, Kaplan B, Kukuy OL, Arad M, Magen H, Shavit-Stein E, Dori A, Livneh A
Int J Mol Sci 2023 Feb 28;24(5) doi: 10.3390/ijms24054655. PMID: 36902083Free PMC Article
Zhang Y, Feng L
J Cutan Med Surg 2022 Sep-Oct;26(5):541. Epub 2021 Dec 8 doi: 10.1177/12034754211064314. PMID: 34878924
Kaku M, Berk JL
Semin Neurol 2019 Oct;39(5):578-588. Epub 2019 Oct 22 doi: 10.1055/s-0039-1688994. PMID: 31639841
Kuseyri O, Haas D, Lang N, Schäkel K, Bettendorf M
Pediatrics 2017 May;139(5) doi: 10.1542/peds.2016-0170. PMID: 28557715
González-López E, Gallego-Delgado M, Guzzo-Merello G, de Haro-Del Moral FJ, Cobo-Marcos M, Robles C, Bornstein B, Salas C, Lara-Pezzi E, Alonso-Pulpon L, Garcia-Pavia P
Eur Heart J 2015 Oct 7;36(38):2585-94. Epub 2015 Jul 28 doi: 10.1093/eurheartj/ehv338. PMID: 26224076

Therapy

Solís Marquínez MN, García Fernández E, Morís de la Tassa J
Reumatol Clin (Engl Ed) 2019 Sep-Oct;15(5):e39-e40. Epub 2017 Jun 2 doi: 10.1016/j.reuma.2017.04.008. PMID: 28583784
Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Planté-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceição I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T
N Engl J Med 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793. PMID: 29972757
De Benedetti F, Gattorno M, Anton J, Ben-Chetrit E, Frenkel J, Hoffman HM, Koné-Paut I, Lachmann HJ, Ozen S, Simon A, Zeft A, Calvo Penades I, Moutschen M, Quartier P, Kasapcopur O, Shcherbina A, Hofer M, Hashkes PJ, Van der Hilst J, Hara R, Bujan-Rivas S, Constantin T, Gul A, Livneh A, Brogan P, Cattalini M, Obici L, Lheritier K, Speziale A, Junge G
N Engl J Med 2018 May 17;378(20):1908-1919. doi: 10.1056/NEJMoa1706314. PMID: 29768139
Weidner T, Illing T, Elsner P
Am J Clin Dermatol 2017 Oct;18(5):629-642. doi: 10.1007/s40257-017-0278-9. PMID: 28342017
Rocha A, Lobato L
Transplant Rev (Orlando) 2017 Apr;31(2):115-120. Epub 2016 Sep 14 doi: 10.1016/j.trre.2016.09.002. PMID: 27671053

Prognosis

Goldis R, Kaplan B, Kukuy OL, Arad M, Magen H, Shavit-Stein E, Dori A, Livneh A
Int J Mol Sci 2023 Feb 28;24(5) doi: 10.3390/ijms24054655. PMID: 36902083Free PMC Article
Lioncino M, Monda E, Palmiero G, Caiazza M, Vetrano E, Rubino M, Esposito A, Salerno G, Dongiglio F, D'Onofrio B, Verrillo F, Cerciello G, Manganelli F, Pacileo G, Bossone E, Golino P, Calabrò P, Limongelli G
Heart Fail Clin 2022 Jan;18(1):73-87. Epub 2021 Oct 25 doi: 10.1016/j.hfc.2021.07.006. PMID: 34776085
Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Planté-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceição I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T
N Engl J Med 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793. PMID: 29972757
Nuvolone M, Merlini G
Nephrol Dial Transplant 2017 May 1;32(5):770-780. doi: 10.1093/ndt/gfw305. PMID: 27540044
Casini A, de Moerloose P
Haemophilia 2016 Sep;22(5):667-75. Epub 2016 Jun 13 doi: 10.1111/hae.12967. PMID: 27293018

Clinical prediction guides

Neculae G, Adam R, Jercan A, Bădeliță S, Tjahjadi C, Draghici M, Stan C, Bax JJ, Popescu BA, Marsan NA, Coriu D, Jurcuț R
ESC Heart Fail 2024 Oct;11(5):2825-2834. Epub 2024 May 16 doi: 10.1002/ehf2.14852. PMID: 38757395Free PMC Article
Fernandes F, Alencar Neto AC, Bueno BVK, Cafezeiro CRF, Rissato JH, Szor RS, Carvalho MLP, Mathias Júnior W, Lino AMM, Castelli JB, Souza EO, Ramires FJA, Hotta VT, Soares Júnior J, Tavares CAM, Krieger JE, Rochitte CE, Dabarian A, Hajjar LA, Kalil Filho R, Mady C
Arq Bras Cardiol 2022 Feb;118(2):422-432. doi: 10.36660/abc.20201003. PMID: 35262576Free PMC Article
Cheong EN, Paik W, Choi YC, Lim YM, Kim H, Shim WH, Park HJ
Yonsei Med J 2021 May;62(5):431-438. doi: 10.3349/ymj.2021.62.5.431. PMID: 33908214Free PMC Article
Benson MD, Waddington-Cruz M, Berk JL, Polydefkis M, Dyck PJ, Wang AK, Planté-Bordeneuve V, Barroso FA, Merlini G, Obici L, Scheinberg M, Brannagan TH 3rd, Litchy WJ, Whelan C, Drachman BM, Adams D, Heitner SB, Conceição I, Schmidt HH, Vita G, Campistol JM, Gamez J, Gorevic PD, Gane E, Shah AM, Solomon SD, Monia BP, Hughes SG, Kwoh TJ, McEvoy BW, Jung SW, Baker BF, Ackermann EJ, Gertz MA, Coelho T
N Engl J Med 2018 Jul 5;379(1):22-31. doi: 10.1056/NEJMoa1716793. PMID: 29972757
Venkatesh P, Selvan H, Singh SB, Gupta D, Kashyap S, Temkar S, Gogia V, Tripathy K, Chawla R, Vohra R
Ophthalmology 2017 Jul;124(7):1014-1022. Epub 2017 Apr 12 doi: 10.1016/j.ophtha.2017.03.011. PMID: 28412068

Recent systematic reviews

Khan LA, Shaikh FH, Khan MS, Zafar B, Farooqi M, Bold B, Aslam HM, Essam N, Noor I, Siddique A, Shakil S, Keen MA
Curr Probl Cardiol 2024 Dec;49(12):102860. Epub 2024 Sep 19 doi: 10.1016/j.cpcardiol.2024.102860. PMID: 39306149
Weidner T, Illing T, Elsner P
Am J Clin Dermatol 2017 Oct;18(5):629-642. doi: 10.1007/s40257-017-0278-9. PMID: 28342017
Kaltoft B, Schmidt G, Lauritzen AF, Gimsing P
Dan Med J 2013 Nov;60(11):A4727. PMID: 24192243

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