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GCGR-related hyperglucagonemia(MVAH)

MedGen UID:
1677024
Concept ID:
C4763635
Disease or Syndrome
Synonyms: ALPHA-CELL HYPERPLASIA WITH GLUCAGONEMIA; Mahvash disease
SNOMED CT: Mahvash disease (1228875006); GCGR-related hyperglucagonemia (1228875006); Glucagon receptor-related hyperglucagonemia (1228875006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): GCGR (17q25.3)
 
Monarch Initiative: MONDO:0018582
OMIM®: 619290
Orphanet: ORPHA438274

Definition

Mahvash disease (MVAH) is an autosomal recessive disorder caused by inactivating mutations in the glucagon receptor, leading to alpha-cell hyperplasia of the pancreas, hyperglucagonemia without glucagonoma syndrome, and occasional hypoglycemia. The disease may lead to glucagonomas and/or primitive neuroectodermal tumors (PNETs). [from OMIM]

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Palpitations
MedGen UID:
14579
Concept ID:
C0030252
Finding
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
Pancreatic alpha-cell hyperplasia
MedGen UID:
1800812
Concept ID:
C5558401
Finding
A diffuse and specific increase in the number of alpha-cells.
Vertigo
MedGen UID:
53006
Concept ID:
C0042571
Sign or Symptom
An abnormal sensation of spinning while the body is actually stationary.
Recurrent pancreatitis
MedGen UID:
1639431
Concept ID:
C4551632
Disease or Syndrome
A recurrent form of pancreatitis.
Type 2 diabetes mellitus
MedGen UID:
41523
Concept ID:
C0011860
Disease or Syndrome
WFS1 spectrum disorder (WFS1-SD) comprises classic WFS1 spectrum disorder and nonclassic WFS1 spectrum disorder. Classic WFS1-SD, a progressive neurodegenerative disorder, is characterized by onset of diabetes mellitus and optic atrophy before age 16 years. Additional complications may include one or more of the following: variable hearing impairment / deafness, diabetes insipidus, neurologic abnormalities, neurogenic bladder, and psychiatric abnormalities. Nonclassic WFS1-SD is less common than classic WFS1-SD. Phenotypes that appear to be milder than classic WFS1-SD include: optic atrophy and hearing impairment; neonatal diabetes, profound congenital deafness, and cataracts; isolated diabetes mellitus; isolated congenital cataracts; and isolated congenital, slowly progressive, and low-frequency (<2000 Hz) sensorineural hearing loss.
Increased glucagon level
MedGen UID:
717776
Concept ID:
C1295677
Finding
An elevated concentration of glucagon in the blood circulation.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGCGR-related hyperglucagonemia

Professional guidelines

PubMed

Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB
Diabetes Care 2015 Sep;38(9):1687-93. Epub 2015 Jun 15 doi: 10.2337/dc15-0843. PMID: 26078479Free PMC Article
Rafacho A, Ortsäter H, Nadal A, Quesada I
J Endocrinol 2014 Dec;223(3):R49-62. Epub 2014 Sep 30 doi: 10.1530/JOE-14-0373. PMID: 25271217
Williams G, Ghatei M, Burrin J, Bloom S
Br Med J (Clin Res Ed) 1986 Jun 21;292(6536):1637-8. doi: 10.1136/bmj.292.6536.1637. PMID: 3087554Free PMC Article

Recent clinical studies

Etiology

Chai S, Zhang R, Zhang Y, Carr RD, Zheng Y, Rajpathak S, Ji L
Front Endocrinol (Lausanne) 2022;13:994944. Epub 2022 Oct 12 doi: 10.3389/fendo.2022.994944. PMID: 36313782Free PMC Article
Ye J
Front Med 2021 Jun;15(3):372-382. Epub 2021 May 28 doi: 10.1007/s11684-021-0862-5. PMID: 34047935
Morita Y, Ohno H, Kobuke K, Oki K, Yoneda M
Endocr J 2021 Jan 28;68(1):95-102. Epub 2020 Sep 10 doi: 10.1507/endocrj.EJ20-0366. PMID: 32908087
Valaiyapathi B, Gower B, Ashraf AP
Curr Diabetes Rev 2020;16(3):220-229. doi: 10.2174/1573399814666180608074510. PMID: 29879890Free PMC Article
Horie I, Haraguchi A, Sako A, Akeshima J, Niri T, Shigeno R, Ito A, Nozaki A, Natsuda S, Akazawa S, Mori Y, Ando T, Kawakami A, Abiru N
Diabetes Res Clin Pract 2018 Oct;144:161-170. Epub 2018 Sep 6 doi: 10.1016/j.diabres.2018.08.015. PMID: 30194951

Diagnosis

Ye J
Front Med 2021 Jun;15(3):372-382. Epub 2021 May 28 doi: 10.1007/s11684-021-0862-5. PMID: 34047935
Valaiyapathi B, Gower B, Ashraf AP
Curr Diabetes Rev 2020;16(3):220-229. doi: 10.2174/1573399814666180608074510. PMID: 29879890Free PMC Article
Ashcroft FM, Rorsman P
Nat Rev Endocrinol 2013 Nov;9(11):660-9. Epub 2013 Sep 17 doi: 10.1038/nrendo.2013.166. PMID: 24042324Free PMC Article
Kovács RK, Korom I, Dobozy A, Farkas G, Ormos J, Kemény L
J Cutan Pathol 2006 Mar;33(3):242-5. doi: 10.1111/j.0303-6987.2006.00408.x. PMID: 16466513
Abe H, Kubota K, Noie T, Kimura W, Makuuchi M
Am J Gastroenterol 1999 May;94(5):1397-401. doi: 10.1111/j.1572-0241.1999.01094.x. PMID: 10235226

Therapy

Wewer Albrechtsen NJ
Peptides 2018 Feb;100:42-47. doi: 10.1016/j.peptides.2017.11.016. PMID: 29412830
Scott RV, Bloom SR
Peptides 2018 Feb;100:36-41. doi: 10.1016/j.peptides.2017.11.013. PMID: 29412829Free PMC Article
Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB
Diabetes Care 2015 Sep;38(9):1687-93. Epub 2015 Jun 15 doi: 10.2337/dc15-0843. PMID: 26078479Free PMC Article
Ashcroft FM, Rorsman P
Nat Rev Endocrinol 2013 Nov;9(11):660-9. Epub 2013 Sep 17 doi: 10.1038/nrendo.2013.166. PMID: 24042324Free PMC Article
Raskin P, Unger RH
Med Clin North Am 1978 Jul;62(4):713-22. doi: 10.1016/s0025-7125(16)31767-9. PMID: 355737

Prognosis

Winther-Sørensen M, Garcia SL, Bartholdy A, Ottenheijm ME, Banasik K, Brunak S, Sørensen CM, Gluud LL, Knop FK, Holst JJ, Rosenkilde MM, Jensen MK, Wewer Albrechtsen NJ
Diabetologia 2024 Aug;67(8):1602-1615. Epub 2024 May 6 doi: 10.1007/s00125-024-06160-1. PMID: 38705923Free PMC Article
Maruszczak K, Radzikowski K, Schütz S, Mangge H, Bergsten P, Forslund A, Manell H, Pixner T, Ahlström H, Kullberg J, Mörwald K, Weghuber D
Front Endocrinol (Lausanne) 2022;13:1004128. Epub 2022 Sep 5 doi: 10.3389/fendo.2022.1004128. PMID: 36133310Free PMC Article
Kobayashi M, Waki H, Nakayama H, Miyachi A, Mieno E, Hamajima H, Goto M, Yamada K, Yamauchi T, Kadowaki T, Kitamura T
J Diabetes Investig 2021 Feb;12(2):286-289. Epub 2020 Jul 17 doi: 10.1111/jdi.13325. PMID: 32548980Free PMC Article
Horie I, Haraguchi A, Sako A, Akeshima J, Niri T, Shigeno R, Ito A, Nozaki A, Natsuda S, Akazawa S, Mori Y, Ando T, Kawakami A, Abiru N
Diabetes Res Clin Pract 2018 Oct;144:161-170. Epub 2018 Sep 6 doi: 10.1016/j.diabres.2018.08.015. PMID: 30194951
Kopple JD
J Nutr 1999 Jan;129(1S Suppl):247S-251S. doi: 10.1093/jn/129.1.247S. PMID: 9915908

Clinical prediction guides

Wewer Albrechtsen NJ, Holst JJ, Cherrington AD, Finan B, Gluud LL, Dean ED, Campbell JE, Bloom SR, Tan TM, Knop FK, Müller TD
Diabetologia 2023 Aug;66(8):1378-1394. Epub 2023 Jun 27 doi: 10.1007/s00125-023-05947-y. PMID: 37367959
Wewer Albrechtsen NJ, Kuhre RE, Pedersen J, Knop FK, Holst JJ
Biomark Med 2016 Nov;10(11):1141-1151. Epub 2016 Sep 9 doi: 10.2217/bmm-2016-0090. PMID: 27611762
Unger RH, Roth MG
Cell Metab 2015 Jan 6;21(1):15-20. Epub 2014 Nov 20 doi: 10.1016/j.cmet.2014.10.011. PMID: 25456738
Holst JJ, Christensen M, Lund A, de Heer J, Svendsen B, Kielgast U, Knop FK
Diabetes Obes Metab 2011 Oct;13 Suppl 1:89-94. doi: 10.1111/j.1463-1326.2011.01452.x. PMID: 21824261
Kovács RK, Korom I, Dobozy A, Farkas G, Ormos J, Kemény L
J Cutan Pathol 2006 Mar;33(3):242-5. doi: 10.1111/j.0303-6987.2006.00408.x. PMID: 16466513

Recent systematic reviews

Chai S, Zhang R, Zhang Y, Carr RD, Zheng Y, Rajpathak S, Ji L
Front Endocrinol (Lausanne) 2022;13:994944. Epub 2022 Oct 12 doi: 10.3389/fendo.2022.994944. PMID: 36313782Free PMC Article
Valaiyapathi B, Gower B, Ashraf AP
Curr Diabetes Rev 2020;16(3):220-229. doi: 10.2174/1573399814666180608074510. PMID: 29879890Free PMC Article

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