title: GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: Masquerading as Rett syndrome-like phenotype.
abstract: There have been a few reports of GM3 synthase deficiency since the disease of the ganglioside biosynthetic pathway was first reported in 2004. It is characterized by infantile-onset epilepsy with severe intellectual disability, blindness, cutaneous dyspigmentation, and choreoathetosis. Here we report the cases of two Korean female siblings with ST3GAL5 variants, who presented with a Rett-like phenotype. They had delayed speech, hand stereotypies with a loss of purposeful hand movements, and choreoathetosis, but no clinical seizures. One of them had microcephaly, while the other had small head circumference less than 10th centile. There were no abnormal laboratory findings with the exception of a high lactate level. MECP2/CDKL5/FOXG1 genetic tests with an array comparative genomic hybridization revealed no molecular defects. Through whole-exome sequencing of the proband, we found compound heterozygous ST3GAL5 variants (p.Gly201Arg and p.Cys195Ser), both of which were novel. The siblings were the same compound heterozygotes and their unaffected parents were heterozygous carriers of each variant. Liquid chromatography-mass spectrometry analysis confirmed a low level of GM3 and its downstream metabolites, indicating GM3 synthase deficiency. These cases expanded the clinical and genetic spectrum of the ultra-rare disease, GM3 synthase deficiency with ST3GAL5 variants. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Byung Chan
authors.initials: BC
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Ki Joong
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Gyeonggi-do, Korea.
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Murim
authors.initials: M
authors.lastname: Choi
authors.affiliation: Department of Pediatrics, Seoul National University College of Medicine, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Chae
mesh_terms: D019943:Amino Acid Substitution; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004827:Epilepsy / Q000175:diagnosis* / Q000235:genetics*; D059472:Exome; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D010375:Pedigree; D010641:Phenotype; D015518:Rett Syndrome / Q000175:diagnosis* / Q000235:genetics*; D012799:Sialyltransferases / Q000172:deficiency* / Q000235:genetics; D035781:Siblings
chemical_list: D012799:Sialyltransferases; C021343:haematoside synthetase
keywords: GM3 synthase; Rett-like phenotype; ST3GAL5; ganglioside; whole-exome sequencing