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Giant axonal neuropathy

MedGen UID:
1684765
Concept ID:
C5200933
Disease or Syndrome
Synonyms: Axonal Neuropathy, Giant; Axonal Neuropathy, Giant (GAN); Giant Axonal Neuropathy; Giant Axonal Neuropathy (GAN); Neuropathy, Giant Axonal; Neuropathy, Giant Axonal (GAN)
SNOMED CT: Giant axonal neuropathy (128207002)
 
Related genes: DCAF8, GAN
 
Monarch Initiative: MONDO:0000128
OMIM®: 256850
OMIM® Phenotypic series: PS256850

Disease characteristics

Excerpted from the GeneReview: GAN-Related Neurodegeneration
GAN-related neurodegeneration comprises a phenotypic continuum ranging from severe (sometimes called classic giant axonal neuropathy) to milder pure early-onset peripheral motor and sensory neuropathies. The classic giant axonal neuropathy phenotype typically manifests as an infantile-onset neurodegenerative disorder, starting as a severe peripheral motor and sensory neuropathy and evolving into central nervous system impairment (intellectual disability, seizures, cerebellar signs, and pyramidal tract signs). Most affected individuals become wheelchair dependent in the second decade of life and eventually bedridden with severe polyneuropathy, ataxia, and dementia. Death usually occurs in the third decade. At the milder end of the spectrum are predominantly motor and sensory neuropathies (with little to no CNS involvement) that overlap with the axonal form of Charcot-Marie-Tooth neuropathies. [from GeneReviews]
Authors:
Puneet Opal   view full author information

Professional guidelines

PubMed

Chen PH, Hu J, Wu J, Huynh DT, Smith TJ, Pan S, Bisnett BJ, Smith AB, Lu A, Condon BM, Chi JT, Boyce M
JCI Insight 2020 Jan 16;5(1) Epub 2019 Nov 26 doi: 10.1172/jci.insight.127751. PMID: 31944090Free PMC Article
Koop O, Schirmacher A, Nelis E, Timmerman V, De Jonghe P, Ringelstein B, Rasic VM, Evrard P, Gärtner J, Claeys KG, Appenzeller S, Rautenstrauss B, Hühne K, Ramos-Arroyo MA, Wörle H, Moilanen JS, Hammans S, Kuhlenbäumer G
Neuromuscul Disord 2007 Aug;17(8):624-30. Epub 2007 Jun 22 doi: 10.1016/j.nmd.2007.03.012. PMID: 17587580
Houlden H, Groves M, Miedzybrodzka Z, Roper H, Willis T, Winer J, Cole G, Reilly MM
J Neurol Neurosurg Psychiatry 2007 Nov;78(11):1267-70. Epub 2007 Jun 19 doi: 10.1136/jnnp.2007.118968. PMID: 17578852Free PMC Article

Recent clinical studies

Etiology

Bharucha-Goebel DX, Norato G, Saade D, Paredes E, Biancavilla V, Donkervoort S, Kaur R, Lehky T, Fink M, Armao D, Gray SJ, Waite M, Debs S, Averion G, Hu Y, Zein WM, Foley AR, Jain M, Bönnemann CG
Brain 2021 Nov 29;144(10):3239-3250. doi: 10.1093/brain/awab179. PMID: 34114613Free PMC Article
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Echaniz-Laguna A, Cuisset JM, Guyant-Marechal L, Aubourg P, Kremer L, Baaloul N, Verloes A, Beladgham K, Perrot J, Francou B, Latour P
Neurogenetics 2020 Jan;21(1):29-37. Epub 2019 Oct 26 doi: 10.1007/s10048-019-00596-z. PMID: 31655922
Yiu EM, Ryan MM
J Peripher Nerv Syst 2012 Sep;17(3):285-300. doi: 10.1111/j.1529-8027.2012.00412.x. PMID: 22971091
Yang Y, Allen E, Ding J, Wang W
Cell Mol Life Sci 2007 Mar;64(5):601-9. doi: 10.1007/s00018-007-6396-4. PMID: 17256086Free PMC Article

Diagnosis

Finsterer J, Löscher WN, Wanschitz J, Iglseder S
J Neuromuscul Dis 2021;8(1):1-23. doi: 10.3233/JND-200518. PMID: 32986679Free PMC Article
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Vijaykumar K, Bindu PS, Taly AB, Mahadevan A, Bharath RD, Gayathri N, Nagappa M, Sinha S
J Child Neurol 2015 Jun;30(7):912-5. Epub 2014 Sep 11 doi: 10.1177/0883073814547721. PMID: 25213662
Hentati F, Hentati E, Amouri R
Handb Clin Neurol 2013;115:933-8. doi: 10.1016/B978-0-444-52902-2.00052-7. PMID: 23931822
Yiu EM, Ryan MM
J Peripher Nerv Syst 2012 Sep;17(3):285-300. doi: 10.1111/j.1529-8027.2012.00412.x. PMID: 22971091

Therapy

Bharucha-Goebel DX, Todd JJ, Saade D, Norato G, Jain M, Lehky T, Bailey RM, Chichester JA, Calcedo R, Armao D, Foley AR, Mohassel P, Tesfaye E, Carlin BP, Seremula B, Waite M, Zein WM, Huryn LA, Crawford TO, Sumner CJ, Hoke A, Heiss JD, Charnas L, Hooper JE, Bouldin TW, Kang EM, Rybin D, Gray SJ, Bönnemann CG; GAN Trial Team
N Engl J Med 2024 Mar 21;390(12):1092-1104. doi: 10.1056/NEJMoa2307952. PMID: 38507752
Yousef M, Bharucha-Goebel D, Saade D, Averion G, Bönnemann CG, Quezado ZMN
A A Pract 2021 Oct 25;15(10):e01539. doi: 10.1213/XAA.0000000000001539. PMID: 34695041
Bharucha-Goebel DX, Norato G, Saade D, Paredes E, Biancavilla V, Donkervoort S, Kaur R, Lehky T, Fink M, Armao D, Gray SJ, Waite M, Debs S, Averion G, Hu Y, Zein WM, Foley AR, Jain M, Bönnemann CG
Brain 2021 Nov 29;144(10):3239-3250. doi: 10.1093/brain/awab179. PMID: 34114613Free PMC Article
Mendell JR, Al-Zaidy SA, Rodino-Klapac LR, Goodspeed K, Gray SJ, Kay CN, Boye SL, Boye SE, George LA, Salabarria S, Corti M, Byrne BJ, Tremblay JP
Mol Ther 2021 Feb 3;29(2):464-488. Epub 2020 Dec 10 doi: 10.1016/j.ymthe.2020.12.007. PMID: 33309881Free PMC Article
Roth LA, Marra JD, LaMarca NH, Sproule DM
J Child Neurol 2015 May;30(6):741-8. Epub 2014 Sep 3 doi: 10.1177/0883073814542946. PMID: 25186661

Prognosis

Echaniz-Laguna A, Cuisset JM, Guyant-Marechal L, Aubourg P, Kremer L, Baaloul N, Verloes A, Beladgham K, Perrot J, Francou B, Latour P
Neurogenetics 2020 Jan;21(1):29-37. Epub 2019 Oct 26 doi: 10.1007/s10048-019-00596-z. PMID: 31655922
Normendez-Martínez MI, Monterde-Cruz L, Martínez R, Marquez-Harper M, Esquitin-Garduño N, Valdes-Flores M, Casas-Avila L, de Leon-Suarez VP, Romero-Díaz VJ, Hidalgo-Bravo A
World J Pediatr 2018 Jun;14(3):298-304. Epub 2018 Jun 6 doi: 10.1007/s12519-018-0140-z. PMID: 29876741
Roth LA, Marra JD, LaMarca NH, Sproule DM
J Child Neurol 2015 May;30(6):741-8. Epub 2014 Sep 3 doi: 10.1177/0883073814542946. PMID: 25186661
Hentati F, Hentati E, Amouri R
Handb Clin Neurol 2013;115:933-8. doi: 10.1016/B978-0-444-52902-2.00052-7. PMID: 23931822
Mahammad S, Murthy SN, Didonna A, Grin B, Israeli E, Perrot R, Bomont P, Julien JP, Kuczmarski E, Opal P, Goldman RD
J Clin Invest 2013 May;123(5):1964-75. Epub 2013 Apr 15 doi: 10.1172/JCI66387. PMID: 23585478Free PMC Article

Clinical prediction guides

Bharucha-Goebel DX, Todd JJ, Saade D, Norato G, Jain M, Lehky T, Bailey RM, Chichester JA, Calcedo R, Armao D, Foley AR, Mohassel P, Tesfaye E, Carlin BP, Seremula B, Waite M, Zein WM, Huryn LA, Crawford TO, Sumner CJ, Hoke A, Heiss JD, Charnas L, Hooper JE, Bouldin TW, Kang EM, Rybin D, Gray SJ, Bönnemann CG; GAN Trial Team
N Engl J Med 2024 Mar 21;390(12):1092-1104. doi: 10.1056/NEJMoa2307952. PMID: 38507752
Bharucha-Goebel DX, Norato G, Saade D, Paredes E, Biancavilla V, Donkervoort S, Kaur R, Lehky T, Fink M, Armao D, Gray SJ, Waite M, Debs S, Averion G, Hu Y, Zein WM, Foley AR, Jain M, Bönnemann CG
Brain 2021 Nov 29;144(10):3239-3250. doi: 10.1093/brain/awab179. PMID: 34114613Free PMC Article
Echaniz-Laguna A, Cuisset JM, Guyant-Marechal L, Aubourg P, Kremer L, Baaloul N, Verloes A, Beladgham K, Perrot J, Francou B, Latour P
Neurogenetics 2020 Jan;21(1):29-37. Epub 2019 Oct 26 doi: 10.1007/s10048-019-00596-z. PMID: 31655922
Soomro A, Alsop RJ, Negishi A, Kreplak L, Fudge D, Kuczmarski ER, Goldman RD, Rheinstädter MC
J R Soc Interface 2017 Apr;14(129) doi: 10.1098/rsif.2017.0123. PMID: 28424304Free PMC Article
Roth LA, Marra JD, LaMarca NH, Sproule DM
J Child Neurol 2015 May;30(6):741-8. Epub 2014 Sep 3 doi: 10.1177/0883073814542946. PMID: 25186661

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