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GM1 gangliosidosis

MedGen UID:
43107
Concept ID:
C0085131
Disease or Syndrome
Synonyms: Beta galactosidase 1 deficiency; GLB 1 deficiency
SNOMED CT: GM1 gangliosidosis (238025006)
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).
 
Related gene: GLB1
 
Monarch Initiative: MONDO:0018149
OMIM®: 230500
Orphanet: ORPHA354

Definition

GM1 gangliosidosis is an inherited disorder that destroys nerve cells (neurons) in the brain and spinal cord. This condition can be classified as one of three major types based on the age at which signs and symptoms first appear. However, the signs and symptoms of these three types can overlap, leading some researchers to believe that GM1 gangliosidosis occurs on a spectrum instead of as three distinct types.

The signs and symptoms of the most severe form of GM1 gangliosidosis, called type I or the infantile form, usually develop by the age of 6 months. Infants with this form of the disorder typically appear normal until their development slows and the muscles used for movement weaken. Affected infants eventually lose the skills they had previously acquired (developmentally regress) and may develop an exaggerated startle reaction to loud noises. Over time, children with GM1 gangliosidosis type I develop an enlarged liver and spleen (hepatosplenomegaly) and skeletal abnormalities. Affected children often  have seizures and profound intellectual disability. 

People with GM1 gangliosidosis type I can lose their vision due to clouding of the clear outer covering of the eye (the cornea) and the breakdown of the light-sensing tissue at the back of the eye (the retina). Affected individuals also develop a red area in the eye known as a cherry-red spot. In some cases, affected individuals have distinctive facial features that are described as "coarse," enlarged gums (gingival hypertrophy), and an enlarged and weakened heart muscle (cardiomyopathy). Individuals with type I usually do not survive past early childhood.

GM1 gangliosidosis type II occurs in one of two forms: the late infantile or the juvenile forms. Children with type II develop normally early in life, but they begin to show signs and symptoms of the condition around the age of 18 months (late infantile form) or 5 years (juvenile form). Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, coarse facial features, or enlarged organs. Type II usually progresses more slowly than type I, but it still  shortens life expectancy. People with the late infantile form typically survive into mid-childhood, while those with the juvenile form may live into early adulthood.

GM1 gangliosidosis type III is the adult or chronic form of the condition, and this is the mildest form. The age at which symptoms first appear varies in people with GM1 gangliosidosis type III, although most affected individuals develop signs and symptoms in their teens. The characteristic features of this type include involuntary tensing of various muscles (dystonia) and abnormalities of the spinal bones (vertebrae). Life expectancy varies among people with GM1 gangliosidosis type III. [from MedlinePlus Genetics]

Professional guidelines

PubMed

Herbst ZM, Hong X, Urdaneta L, Klein T, Waggoner C, Liao HC, Kubaski F, Giugliani R, Fuller M, Gelb MH
Mol Genet Metab 2023 Sep-Oct;140(1-2):107632. Epub 2023 Jun 24 doi: 10.1016/j.ymgme.2023.107632. PMID: 37407323Free PMC Article
Yuskiv N, Higaki K, Stockler-Ipsiroglu S
Int J Mol Sci 2020 Nov 30;21(23) doi: 10.3390/ijms21239121. PMID: 33266180Free PMC Article
Deodato F, Procopio E, Rampazzo A, Taurisano R, Donati MA, Dionisi-Vici C, Caciotti A, Morrone A, Scarpa M
Metab Brain Dis 2017 Oct;32(5):1529-1536. Epub 2017 Jun 3 doi: 10.1007/s11011-017-0044-y. PMID: 28577204

Recent clinical studies

Etiology

Shaimardanova AA, Solovyeva VV, Issa SS, Rizvanov AA
Int J Mol Sci 2023 Feb 11;24(4) doi: 10.3390/ijms24043627. PMID: 36835039Free PMC Article
Luckett A, Yousef M, Tifft C, Jenkins K, Smith A, Munoz A, Quimby R, Porter FD, Dang Do AN
Am J Med Genet A 2023 Mar;191(3):711-717. Epub 2022 Dec 2 doi: 10.1002/ajmg.a.63064. PMID: 36461157Free PMC Article
Arash-Kaps L, Komlosi K, Seegräber M, Diederich S, Paschke E, Amraoui Y, Beblo S, Dieckmann A, Smitka M, Hennermann JB
J Pediatr 2019 Dec;215:152-157.e3. doi: 10.1016/j.jpeds.2019.08.016. PMID: 31761138
Franceschini D, Dinulos JG
Curr Opin Pediatr 2015 Aug;27(4):480-5. doi: 10.1097/MOP.0000000000000247. PMID: 26087431
Suzuki Y
Brain Dev 2013 Jun;35(6):515-23. Epub 2013 Jan 3 doi: 10.1016/j.braindev.2012.12.002. PMID: 23290321

Diagnosis

D'Souza P, Farmer C, Johnston JM, Han ST, Adams D, Hartman AL, Zein W, Huryn LA, Solomon B, King K, Jordan CP, Myles J, Nicoli ER, Rothermel CE, Mojica Algarin Y, Huang R, Quimby R, Zainab M, Bowden S, Crowell A, Buckley A, Brewer C, Regier DS, Brooks BP, Acosta MT, Baker EH, Vézina G, Thurm A, Tifft CJ
Genet Med 2024 Jul;26(7):101144. Epub 2024 Apr 16 doi: 10.1016/j.gim.2024.101144. PMID: 38641994Free PMC Article
Akar HT, Yıldız Y, Güvenkaya G, Çıkı K, Kahraman AB, Erdal İ, Coşkun T, Dursun A, Sivri HS, Tokatlı A
Balkan Med J 2022 Sep 9;39(5):345-350. Epub 2022 Aug 15 doi: 10.4274/balkanmedj.galenos.2022.2022-3-75. PMID: 35965426Free PMC Article
Zhou H, Wu Z, Wang Y, Wu Q, Hu M, Ma S, Zhou M, Sun Y, Yu B, Ye J, Jiang W, Fu Z, Gong Y
Adv Exp Med Biol 2022;1372:189-213. doi: 10.1007/978-981-19-0394-6_13. PMID: 35503182
Arash-Kaps L, Komlosi K, Seegräber M, Diederich S, Paschke E, Amraoui Y, Beblo S, Dieckmann A, Smitka M, Hennermann JB
J Pediatr 2019 Dec;215:152-157.e3. doi: 10.1016/j.jpeds.2019.08.016. PMID: 31761138
Franceschini D, Dinulos JG
Curr Opin Pediatr 2015 Aug;27(4):480-5. doi: 10.1097/MOP.0000000000000247. PMID: 26087431

Therapy

Allende ML, Lee YT, Byrnes C, Li C, Tuymetova G, Bakir JY, Nicoli ER, James VK, Brodbelt JS, Tifft CJ, Proia RL
J Lipid Res 2023 Dec;64(12):100463. Epub 2023 Oct 21 doi: 10.1016/j.jlr.2023.100463. PMID: 37871851Free PMC Article
Luckett A, Yousef M, Tifft C, Jenkins K, Smith A, Munoz A, Quimby R, Porter FD, Dang Do AN
Am J Med Genet A 2023 Mar;191(3):711-717. Epub 2022 Dec 2 doi: 10.1002/ajmg.a.63064. PMID: 36461157Free PMC Article
Regier DS, Proia RL, D'Azzo A, Tifft CJ
Pediatr Endocrinol Rev 2016 Jun;13 Suppl 1(Suppl 1):663-73. PMID: 27491214Free PMC Article
Suzuki Y
Brain Dev 2013 Jun;35(6):515-23. Epub 2013 Jan 3 doi: 10.1016/j.braindev.2012.12.002. PMID: 23290321
Suzuki Y
Cell Mol Life Sci 2008 Feb;65(3):351-3. doi: 10.1007/s00018-008-7470-2. PMID: 18202827Free PMC Article

Prognosis

Allende ML, Lee YT, Byrnes C, Li C, Tuymetova G, Bakir JY, Nicoli ER, James VK, Brodbelt JS, Tifft CJ, Proia RL
J Lipid Res 2023 Dec;64(12):100463. Epub 2023 Oct 21 doi: 10.1016/j.jlr.2023.100463. PMID: 37871851Free PMC Article
Lang FM, Korner P, Harnett M, Karunakara A, Tifft CJ
Mol Genet Metab 2020 Mar;129(3):228-235. Epub 2019 Dec 30 doi: 10.1016/j.ymgme.2019.12.012. PMID: 31937438Free PMC Article
Arash-Kaps L, Komlosi K, Seegräber M, Diederich S, Paschke E, Amraoui Y, Beblo S, Dieckmann A, Smitka M, Hennermann JB
J Pediatr 2019 Dec;215:152-157.e3. doi: 10.1016/j.jpeds.2019.08.016. PMID: 31761138
Feng Y, Huang Y, Zhao X, Sheng H, Feng Y, Zhang W, Liu L
Metab Brain Dis 2018 Dec;33(6):2051-2057. Epub 2018 Sep 28 doi: 10.1007/s11011-018-0315-2. PMID: 30267299
Franceschini D, Dinulos JG
Curr Opin Pediatr 2015 Aug;27(4):480-5. doi: 10.1097/MOP.0000000000000247. PMID: 26087431

Clinical prediction guides

D'Souza P, Farmer C, Johnston JM, Han ST, Adams D, Hartman AL, Zein W, Huryn LA, Solomon B, King K, Jordan CP, Myles J, Nicoli ER, Rothermel CE, Mojica Algarin Y, Huang R, Quimby R, Zainab M, Bowden S, Crowell A, Buckley A, Brewer C, Regier DS, Brooks BP, Acosta MT, Baker EH, Vézina G, Thurm A, Tifft CJ
Genet Med 2024 Jul;26(7):101144. Epub 2024 Apr 16 doi: 10.1016/j.gim.2024.101144. PMID: 38641994Free PMC Article
Yuskiv N, Higaki K, Stockler-Ipsiroglu S
Int J Mol Sci 2020 Nov 30;21(23) doi: 10.3390/ijms21239121. PMID: 33266180Free PMC Article
Lang FM, Korner P, Harnett M, Karunakara A, Tifft CJ
Mol Genet Metab 2020 Mar;129(3):228-235. Epub 2019 Dec 30 doi: 10.1016/j.ymgme.2019.12.012. PMID: 31937438Free PMC Article
Janikiewicz J, Szymański J, Malinska D, Patalas-Krawczyk P, Michalska B, Duszyński J, Giorgi C, Bonora M, Dobrzyn A, Wieckowski MR
Cell Death Dis 2018 Feb 28;9(3):332. doi: 10.1038/s41419-017-0105-5. PMID: 29491385Free PMC Article
Gimovsky AC, Luzi P, Berghella V
Am J Obstet Gynecol 2015 Mar;212(3):281-90. Epub 2014 Oct 8 doi: 10.1016/j.ajog.2014.10.007. PMID: 25305402

Recent systematic reviews

Iyer NS, Gimovsky AC, Ferreira CR, Critchlow E, Al-Kouatly HB
Clin Genet 2021 Nov;100(5):493-503. Epub 2021 Jul 16 doi: 10.1111/cge.14005. PMID: 34057202
Gimovsky AC, Luzi P, Berghella V
Am J Obstet Gynecol 2015 Mar;212(3):281-90. Epub 2014 Oct 8 doi: 10.1016/j.ajog.2014.10.007. PMID: 25305402

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