Abstract
Background
ST3GAL5 encodes GM3 synthase (ST3 beta-galactoside alpha-2,3-sialyltransferase 5; ST3GAL5),
which synthesizes GM3 by transferring sialic acid to lactosylceramide. GM3, a sialic
acid-containing glycosphingolipid known as ganglioside, is a precursor to the biosynthesis
of various more complex gangliosides that are active in the brain. Biallelic variants
in ST3GAL5 cause GM3 synthase deficiency (GM3SD), a rare congenital disorder of glycosylation.
GM3SD was first identified in the Amish population in 2004.
Case
We report two siblings diagnosed with GM3SD due to novel compound heterozygous ST3GAL5 variants. The novel ST3GAL5 variants, detected by whole-exome sequencing in the patients, were confirmed to be
pathogenic by GM3 synthase assay. The clinical courses of these patients, which began
in infancy with irritability and growth failure, followed by developmental delay and
hearing loss, were consistent with previous case reports of GM3SD. The older sibling
underwent deep brain stimulation for severe involuntary movements at the age of 9 years.
The younger sibling suffered from acute encephalopathy at the age of 9 months and
subsequently developed refractory epilepsy.
Discussion
Reports of GM3SD outside the Amish population are rare, and whole-exome sequencing
may be required to diagnose GM3SD in non-Amish patients. Since an effective treatment
for GM3SD has not yet been established, we might select deep brain stimulation as
a symptomatic treatment for involuntary movements in GM3SD.
Keywords
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Article info
Publication history
Published online: January 21, 2023
Accepted:
January 10,
2023
Received in revised form:
December 24,
2022
Received:
September 13,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.
