TY - JOUR
T1 - Glycogen Storage Disease type IA refractory to cornstarch
T2 - Can next generation sequencing offer a solution?
AU - Steg Saban, Or
AU - Pode-Shakked, Ben
AU - Abu-Libdeh, Bassam
AU - Granot, Maya
AU - Barkai, Galia
AU - Haberman, Yael
AU - Roterman, Inon
AU - Lahad, Avishay
AU - Shouval, Dror S.
AU - Weiss, Batia
AU - Marek-Yagel, Dina
AU - Barel, Ortal
AU - Loberman-Nachum, Nurit
AU - Abraham, Smadar
AU - Somech, Raz
AU - Weinstein, David A.
AU - Anikster, Yair
N1 - Publisher Copyright:
© 2022 Elsevier Masson SAS
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Avoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e.g. genes associated with amylase production) which may explain their persistent symptoms. WES confirmed the GSD-Ia diagnosis, with all three probands harboring the homozygous p.R83C variant in G6PC. While no other significant variants were identified for patients A and B, a homozygous p.G276V variant in the SI gene was detected in patient C, establishing the dual-diagnosis of GSD-Ia and Sucrase-Isomaltase Deficiency. To conclude, we suggest that WES should be considered in GSD-Ia patients who show persistent symptoms despite optimal dietary management.
AB - Avoidance of fasting and regular ingestion of uncooked-cornstarch have long been the mainstay dietary treatment of Glycogen Storage Disease type Ia (GSD-Ia). However, GSD-Ia patients who despite optimal dietary treatment show poor glycemic control and are intolerant to cornstarch, present a complex clinical challenge. We pursued Whole Exome Sequencing (WES) in three such unrelated patients, to both confirm a molecular diagnosis of GSD-Ia, and seek additional variants in other genes (e.g. genes associated with amylase production) which may explain their persistent symptoms. WES confirmed the GSD-Ia diagnosis, with all three probands harboring the homozygous p.R83C variant in G6PC. While no other significant variants were identified for patients A and B, a homozygous p.G276V variant in the SI gene was detected in patient C, establishing the dual-diagnosis of GSD-Ia and Sucrase-Isomaltase Deficiency. To conclude, we suggest that WES should be considered in GSD-Ia patients who show persistent symptoms despite optimal dietary management.
KW - Exome sequencing
KW - Glycogen storage disease
KW - Sucrase isomaltase deficiency
KW - Uncooked cornstarch
UR - https://www.scopus.com/pages/publications/85130360676
U2 - 10.1016/j.ejmg.2022.104518
DO - 10.1016/j.ejmg.2022.104518
M3 - Article
C2 - 35550444
AN - SCOPUS:85130360676
SN - 1769-7212
VL - 65
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 6
M1 - 104518
ER -