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Amyloidosis, hereditary systemic 6(AMYLD6)

MedGen UID:
1860723
Concept ID:
C5935573
Disease or Syndrome
Synonyms: AMYLD6; AMYLOIDOSIS, HEREDITARY SYSTEMIC 6
 
Gene (location): B2M (15q21.1)
 
Monarch Initiative: MONDO:0971010
OMIM®: 620659

Definition

Hereditary systemic amyloidosis-6 (AMYLD6) is an autosomal dominant systemic amyloidosis characterized by onset in middle age of gastrointestinal and cardiac symptoms resulting from progressive amyloid deposition. Neurologic involvement, sicca syndrome, and carpal tunnel syndrome may also be present (summary by Prokaeva et al., 2022 and Haslett et al., 2023). For a discussion of genetic heterogeneity of hereditary systemic amyloidosis, see AMYLD1 (105210). [from OMIM]

Clinical features

From HPO
Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Reduction of total body weight.
Hepatic amyloidosis
MedGen UID:
75642
Concept ID:
C0267839
Disease or Syndrome
A form of amyloidosis that affects the liver.
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Orthostatic hypotension
MedGen UID:
43803
Concept ID:
C0020651
Disease or Syndrome
A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position.
Polyneuropathy
MedGen UID:
57502
Concept ID:
C0152025
Disease or Syndrome
A generalized disorder of peripheral nerves.
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Cardiac amyloidosis
MedGen UID:
488730
Concept ID:
C0268407
Disease or Syndrome
Extracellular deposition in cardiac tissue of a proteinaceous material that, when stained with Congo red, demonstrates apple-green birefringence under polarized light and that has a distinct color when stained with sulfated Alcian blue. Viewed with electron microscopy, the amyloid deposits are seen to be composed of a beta-sheet fibrillar material. These nonbranching fibrils have a diameter of 7.5 to 10 nm and are the result of protein misfolding.
Amyloidosis of peripheral nerves
MedGen UID:
867772
Concept ID:
C4022162
Disease or Syndrome
The presence of amyloid deposition in the nerves of the peripheral nervous system.

Professional guidelines

PubMed

Johnson SR, Shaw DE, Avoseh M, Soomro I, Pointon KS, Kokosi M, Nicholson AG, Desai SR, George PM
Thorax 2024 Mar 15;79(4):366-377. doi: 10.1136/thorax-2022-219738. PMID: 38182428
Carroll A, Dyck PJ, de Carvalho M, Kennerson M, Reilly MM, Kiernan MC, Vucic S
J Neurol Neurosurg Psychiatry 2022 Jun;93(6):668-678. Epub 2022 Mar 7 doi: 10.1136/jnnp-2021-327909. PMID: 35256455Free PMC Article
Adams D, Ando Y, Beirão JM, Coelho T, Gertz MA, Gillmore JD, Hawkins PN, Lousada I, Suhr OB, Merlini G
J Neurol 2021 Jun;268(6):2109-2122. Epub 2020 Jan 6 doi: 10.1007/s00415-019-09688-0. PMID: 31907599Free PMC Article

Recent clinical studies

Etiology

Dang J, Ferlicot S, Misrahi M, Mussini C, Kounis I, Rémy P, Samuel D, Planté-Bordeneuve V, Adams D, Funalot B, Snanoudj R, Damy T, Moktefi A, Audard V, Zaidan M
Nephrol Dial Transplant 2023 Aug 31;38(9):2019-2030. doi: 10.1093/ndt/gfad006. PMID: 36646436
Kozycki CT, Kodati S, Huryn L, Wang H, Warner BM, Jani P, Hammoud D, Abu-Asab MS, Jittayasothorn Y, Mattapallil MJ, Tsai WL, Ullah E, Zhou P, Tian X, Soldatos A, Moutsopoulos N, Kao-Hsieh M, Heller T, Cowen EW, Lee CR, Toro C, Kalsi S, Khavandgar Z, Baer A, Beach M, Long Priel D, Nehrebecky M, Rosenzweig S, Romeo T, Deuitch N, Brenchley L, Pelayo E, Zein W, Sen N, Yang AH, Farley G, Sweetser DA, Briere L, Yang J, de Oliveira Poswar F, Schwartz IVD, Silva Alves T, Dusser P, Koné-Paut I, Touitou I, Titah SM, van Hagen PM, van Wijck RTA, van der Spek PJ, Yano H, Benneche A, Apalset EM, Jansson RW, Caspi RR, Kuhns DB, Gadina M, Takada H, Ida H, Nishikomori R, Verrecchia E, Sangiorgi E, Manna R, Brooks BP, Sobrin L, Hufnagel RB, Beck D, Shao F, Ombrello AK, Aksentijevich I, Kastner DL; Undiagnosed Diseases Network
Ann Rheum Dis 2022 Oct;81(10):1453-1464. Epub 2022 Jul 22 doi: 10.1136/annrheumdis-2022-222629. PMID: 35868845Free 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
Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, Klarich KW, Miller WL, Maleszewski JJ, Dispenzieri A
J Am Coll Cardiol 2016 Sep 6;68(10):1014-20. doi: 10.1016/j.jacc.2016.06.033. PMID: 27585505
Shin SC, Robinson-Papp J
Mt Sinai J Med 2012 Nov-Dec;79(6):733-48. doi: 10.1002/msj.21352. PMID: 23239211Free PMC Article

Diagnosis

Johnson SR, Shaw DE, Avoseh M, Soomro I, Pointon KS, Kokosi M, Nicholson AG, Desai SR, George PM
Thorax 2024 Mar 15;79(4):366-377. doi: 10.1136/thorax-2022-219738. PMID: 38182428
Carroll A, Dyck PJ, de Carvalho M, Kennerson M, Reilly MM, Kiernan MC, Vucic S
J Neurol Neurosurg Psychiatry 2022 Jun;93(6):668-678. Epub 2022 Mar 7 doi: 10.1136/jnnp-2021-327909. PMID: 35256455Free PMC Article
Adams D, Ando Y, Beirão JM, Coelho T, Gertz MA, Gillmore JD, Hawkins PN, Lousada I, Suhr OB, Merlini G
J Neurol 2021 Jun;268(6):2109-2122. Epub 2020 Jan 6 doi: 10.1007/s00415-019-09688-0. PMID: 31907599Free PMC Article
Oldham J, Lachmann HJ
Clin Exp Dermatol 2020 Dec;45(8):967-973. Epub 2020 Sep 3 doi: 10.1111/ced.14251. PMID: 32882069
Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, Klarich KW, Miller WL, Maleszewski JJ, Dispenzieri A
J Am Coll Cardiol 2016 Sep 6;68(10):1014-20. doi: 10.1016/j.jacc.2016.06.033. PMID: 27585505

Therapy

Oldham J, Lachmann HJ
Clin Exp Dermatol 2020 Dec;45(8):967-973. Epub 2020 Sep 3 doi: 10.1111/ced.14251. PMID: 32882069
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
Carvalho A, Rocha A, Lobato L
Liver Transpl 2015 Mar;21(3):282-92. Epub 2015 Feb 2 doi: 10.1002/lt.24058. PMID: 25482846
Jono H, Anno T, Motoyama K, Misumi Y, Tasaki M, Oshima T, Mori Y, Mizuguchi M, Ueda M, Shinriki S, Shono M, Obayashi K, Arima H, Ando Y
Amyloid 2012 Jun;19 Suppl 1:50-2. doi: 10.3109/13506129.2012.674988. PMID: 22620966
Baures PW, Peterson SA, Kelly JW
Bioorg Med Chem 1998 Aug;6(8):1389-401. doi: 10.1016/s0968-0896(98)00130-8. PMID: 9784876

Prognosis

Johnson SR, Shaw DE, Avoseh M, Soomro I, Pointon KS, Kokosi M, Nicholson AG, Desai SR, George PM
Thorax 2024 Mar 15;79(4):366-377. doi: 10.1136/thorax-2022-219738. PMID: 38182428
Kozycki CT, Kodati S, Huryn L, Wang H, Warner BM, Jani P, Hammoud D, Abu-Asab MS, Jittayasothorn Y, Mattapallil MJ, Tsai WL, Ullah E, Zhou P, Tian X, Soldatos A, Moutsopoulos N, Kao-Hsieh M, Heller T, Cowen EW, Lee CR, Toro C, Kalsi S, Khavandgar Z, Baer A, Beach M, Long Priel D, Nehrebecky M, Rosenzweig S, Romeo T, Deuitch N, Brenchley L, Pelayo E, Zein W, Sen N, Yang AH, Farley G, Sweetser DA, Briere L, Yang J, de Oliveira Poswar F, Schwartz IVD, Silva Alves T, Dusser P, Koné-Paut I, Touitou I, Titah SM, van Hagen PM, van Wijck RTA, van der Spek PJ, Yano H, Benneche A, Apalset EM, Jansson RW, Caspi RR, Kuhns DB, Gadina M, Takada H, Ida H, Nishikomori R, Verrecchia E, Sangiorgi E, Manna R, Brooks BP, Sobrin L, Hufnagel RB, Beck D, Shao F, Ombrello AK, Aksentijevich I, Kastner DL; Undiagnosed Diseases Network
Ann Rheum Dis 2022 Oct;81(10):1453-1464. Epub 2022 Jul 22 doi: 10.1136/annrheumdis-2022-222629. PMID: 35868845Free PMC Article
Carroll A, Dyck PJ, de Carvalho M, Kennerson M, Reilly MM, Kiernan MC, Vucic S
J Neurol Neurosurg Psychiatry 2022 Jun;93(6):668-678. Epub 2022 Mar 7 doi: 10.1136/jnnp-2021-327909. PMID: 35256455Free PMC Article
Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, Klarich KW, Miller WL, Maleszewski JJ, Dispenzieri A
J Am Coll Cardiol 2016 Sep 6;68(10):1014-20. doi: 10.1016/j.jacc.2016.06.033. PMID: 27585505
Shin SC, Robinson-Papp J
Mt Sinai J Med 2012 Nov-Dec;79(6):733-48. doi: 10.1002/msj.21352. PMID: 23239211Free PMC Article

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
Dang J, Ferlicot S, Misrahi M, Mussini C, Kounis I, Rémy P, Samuel D, Planté-Bordeneuve V, Adams D, Funalot B, Snanoudj R, Damy T, Moktefi A, Audard V, Zaidan M
Nephrol Dial Transplant 2023 Aug 31;38(9):2019-2030. doi: 10.1093/ndt/gfad006. PMID: 36646436
Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, Klarich KW, Miller WL, Maleszewski JJ, Dispenzieri A
J Am Coll Cardiol 2016 Sep 6;68(10):1014-20. doi: 10.1016/j.jacc.2016.06.033. PMID: 27585505
Sen-Chowdhry S, Syrris P, McKenna WJ
Heart Fail Clin 2010 Apr;6(2):179-86. doi: 10.1016/j.hfc.2009.11.005. PMID: 20347786
Sandgren O, Kjellgren D, Suhr OB
Acta Ophthalmol 2008 Aug;86(5):520-4. Epub 2008 Apr 24 doi: 10.1111/j.1600-0420.2007.01098.x. PMID: 18435819

Recent systematic reviews

Dohrn MF, Ihne S, Hegenbart U, Medina J, Züchner SL, Coelho T, Hahn K
J Neurochem 2021 Mar;156(6):802-818. Epub 2020 Dec 3 doi: 10.1111/jnc.15233. PMID: 33155274
Xin Y, Hu W, Chen X, Hu J, Sun Y, Zhao Y
Hellenic J Cardiol 2019 Nov-Dec;60(6):375-383. Epub 2019 Feb 8 doi: 10.1016/j.hjc.2019.01.015. PMID: 30742933

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