Amish, Mennonite, and Hutterite
Genetic Disorder Database

GM3 synthase deficiency

Disorder
OMIM #: #609056  (Click to access OMIM database)
Disorder: GM3 synthase deficiency 
Also known as: AMISH INFANTILE EPILEPSY SYNDROME
EPILEPSY SYNDROME, INFANTILE-ONSET SYMPTOMATIC
SALT AND PEPPER DEVELOPMENTAL REGRESSION SYNDROME 
Clinical
Phenotype: generalized clonic-tonic seizures, hypotonia, cerebral atrophy, myoclonus, developmental delay, developmental regression, motor delay, blindness, optic atrophy, hyperpigmented skin (macules), irritability, feeding difficulties, failure to thrive, vomiting, 
Seen In: Amish
Old Order Mennonite
Old Colony Mennonite
Unknown/Other Mennonite
Hutterite
Remarks: Autosomal recessive 
Mutations
1   Amish  
Gene: ST3GAL5
Base Change: C>T, at nucleotide 862
Amino Acid Change: arg 288 --> term
Last updated: 2022-12-08 

References
Aoki K, Heaps AD, Strauss KA, Tiemeyer M. (2019) Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency. Clin Mass Spectrom Mar 16;14 Pt B:106-114.
PubMed ID: 34917767 
Bowser LE, Young M, Wenger OK, Ammous Z, Brigatti KW, Carson VJ, Moser T, Deline J, Aoki K, Morlet T, Scott EM, Puffenberger EG, Robinson DL, Hendrickson C, Salvin J, Gottlieb S, Heaps AD, Tiemeyer M, Strauss KA. (2019) Recessive GM3 synthase deficiency: Natural history, biochemistry, and therapeutic frontier. Mol Genet Metab Apr;126(4):475-488.
PubMed ID: 30691927 
Farukhi F, Dakkouri C, Wang H, Wiztnitzer M, Traboulsi EI. (2006) Etiology of vision loss in ganglioside GM3 synthase deficiency. Ophthalmic Genet Sep;27(3):89-91.
PubMed ID: 17050284 
Simpson MA, Cross H, Proukakis C, Priestman DA, Neville DC, Reinkensmeier G, Wang H, Wiznitzer M, Gurtz K, Verganelaki A, Pryde A, Patton MA, Dwek RA, Butters TD, Platt FM, and Crosby AH. (2004) Infantile-onset symptomatic epilepsy syndrome caused by a homozygous loss-of-function mutation of GM3 synthase. Nat Genet 36(11): 1225-1229.
PubMed ID: 15502825 
Strauss KA, Gonzaga-Jauregui C, Brigatti KW, Williams KB, King AK, Van Hout C, Robinson DL, Young M, Praveen K, Heaps AD, Kuebler M, Baras A, Reid JG, Overton JD, Dewey FE, Jinks RN, Finnegan I, Mellis SJ, Shuldiner AR, Puffenberger EG. (2018) Genomic diagnostics within a medically underserved population: efficacy and implications. Genet Med Jan;20(1):31-41.
PubMed ID: 28726809 
Wang AS, Kilbane C. (2022) Dystonia Due to GM3 Synthase Deficiency. Mov Disord Clin Pract Jan 5;9(2):236-239.
PubMed ID: 35146061 
Wang H, Bright A, Xin B, Bockoven JR, Paller AS. (2013) Cutaneous dyspigmentation in patients with ganglioside GM3 synthase deficiency. Am J Med Genet A Apr;161A(4):875-9.
PubMed ID: 23436467 
Yoshikawa M, Go S, Suzuki SI, Suzuki A, Katori Y, Morlet T, Gottlieb SM, Fujiwara M, Iwasaki K, Strauss KA, Inokuchi JI. (2015) Ganglioside GM3 is essential for the structural integrity and function of cochlear hair cells. Hum Mol Genet May 15;24(10):2796-807.
PubMed ID: 25652401 

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