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Journal Articles Genetics in Medicine Year : 2021

GM3 synthase deficiency in non-Amish patients

D. Gras
  • Function : Author
L. Perrin
  • Function : Author
Y. Capri
  • Function : Author
A. Pervillé
  • Function : Author
L. Arnaud
L. La Selva
  • Function : Author


PURPOSE: Biallelic loss-of-function variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD) responsible for Amish infantile epilepsy syndrome. All Amish patients carry the homozygous p.(Arg288Ter) variant arising from a founder effect. To date only 10 patients from 4 non-Amish families have been reported. Thus, the phenotypical spectrum of GM3SD due to other variants and other genetic backgrounds is still poorly known. METHODS: We collected clinical and molecular data from 16 non-Amish patients with pathogenic ST3GAL5 variants resulting in GM3SD. RESULTS: We identified 12 families originating from Reunion Island, Ivory Coast, Italy, and Algeria and carrying 6 ST3GAL5 variants, 5 of which were novel. Genealogical investigations and/or haplotype analyses showed that 3 of these variants were founder alleles. Glycosphingolipids quantification in patients' plasma confirmed the pathogenicity of 4 novel variants. All patients (N = 16), aged 2 to 12 years, had severe to profound intellectual disability, 14 of 16 had a hyperkinetic movement disorder, 11 of 16 had epilepsy and 9 of 16 had microcephaly. Other main features were progressive skin pigmentation anomalies, optic atrophy or pale papillae, and hearing loss. CONCLUSION: The phenotype of non-Amish patients with GM3SD is similar to the Amish infantile epilepsy syndrome, which suggests that GM3SD is associated with a narrow and severe clinical spectrum.
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Dates and versions

inserm-03587211 , version 1 (24-02-2022)



S. Heide, M. L. Jacquemont, D. Cheillan, M. Renouil, M. Tallot, et al.. GM3 synthase deficiency in non-Amish patients. Genetics in Medicine, 2021, 24 (2), pp.492-498. ⟨10.1016/j.gim.2021.10.007⟩. ⟨inserm-03587211⟩
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