TY - JOUR
T1 - Phosphoglucomutase-1 deficiency
T2 - Early presentation, metabolic management and detection in neonatal blood spots
AU - Conte, Federica
AU - Morava, Eva
AU - Bakar, Nurulamin Abu
AU - Wortmann, Saskia B.
AU - Poerink, Anne Jonge
AU - Grunewald, Stephanie
AU - Crushell, Ellen
AU - Al-Gazali, Lihadh
AU - de Vries, Maaike C.
AU - Mørkrid, Lars
AU - Hertecant, Jozef
AU - Brocke Holmefjord, Katja S.
AU - Kronn, David
AU - Feigenbaum, Annette
AU - Fingerhut, Ralph
AU - Wong, Sunnie Y.
AU - van Scherpenzeel, Monique
AU - Voermans, Nicol C.
AU - Lefeber, Dirk J.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Phosphoglucomutase 1 deficiency is a congenital disorder of glycosylation (CDG) with multiorgan involvement affecting carbohydrate metabolism, N-glycosylation and energy production. The metabolic management consists of dietary D-galactose supplementation that ameliorates hypoglycemia, hepatic dysfunction, endocrine anomalies and growth delay. Previous studies suggest that D-galactose administration in juvenile patients leads to more significant and long-lasting effects, stressing the urge of neonatal diagnosis (0–6 months of age). Here, we detail the early clinical presentation of PGM1-CDG in eleven infantile patients, and applied the modified Beutler test for screening of PGM1-CDG in neonatal dried blood spots (DBSs). All eleven infants presented episodic hypoglycemia and elevated transaminases, along with cleft palate and growth delay (10/11), muscle involvement (8/11), neurologic involvement (5/11), cardiac defects (2/11). Standard dietary measures for suspected lactose intolerance in four patients prior to diagnosis led to worsening of hypoglycemia, hepatic failure and recurrent diarrhea, which resolved upon D-galactose supplementation. To investigate possible differences in early vs. late clinical presentation, we performed the first systematic literature review for PGM1-CDG, which highlighted respiratory and gastrointestinal symptoms as significantly more diagnosed in neonatal age. The modified Butler-test successfully identified PGM1-CDG in DBSs from seven patients, including for the first time Guthrie cards from newborn screening, confirming the possibility of future inclusion of PGM1-CDG in neonatal screening programs. In conclusion, severe infantile morbidity of PGM1-CDG due to delayed diagnosis could be prevented by raising awareness on its early presentation and by inclusion in newborn screening programs, enabling early treatments and galactose-based metabolic management.
AB - Phosphoglucomutase 1 deficiency is a congenital disorder of glycosylation (CDG) with multiorgan involvement affecting carbohydrate metabolism, N-glycosylation and energy production. The metabolic management consists of dietary D-galactose supplementation that ameliorates hypoglycemia, hepatic dysfunction, endocrine anomalies and growth delay. Previous studies suggest that D-galactose administration in juvenile patients leads to more significant and long-lasting effects, stressing the urge of neonatal diagnosis (0–6 months of age). Here, we detail the early clinical presentation of PGM1-CDG in eleven infantile patients, and applied the modified Beutler test for screening of PGM1-CDG in neonatal dried blood spots (DBSs). All eleven infants presented episodic hypoglycemia and elevated transaminases, along with cleft palate and growth delay (10/11), muscle involvement (8/11), neurologic involvement (5/11), cardiac defects (2/11). Standard dietary measures for suspected lactose intolerance in four patients prior to diagnosis led to worsening of hypoglycemia, hepatic failure and recurrent diarrhea, which resolved upon D-galactose supplementation. To investigate possible differences in early vs. late clinical presentation, we performed the first systematic literature review for PGM1-CDG, which highlighted respiratory and gastrointestinal symptoms as significantly more diagnosed in neonatal age. The modified Butler-test successfully identified PGM1-CDG in DBSs from seven patients, including for the first time Guthrie cards from newborn screening, confirming the possibility of future inclusion of PGM1-CDG in neonatal screening programs. In conclusion, severe infantile morbidity of PGM1-CDG due to delayed diagnosis could be prevented by raising awareness on its early presentation and by inclusion in newborn screening programs, enabling early treatments and galactose-based metabolic management.
KW - Congenital disorder of glycosylation
KW - Dilated cardiomyopathy
KW - Exercise intolerance
KW - Galactose
KW - Hypoglycemia
KW - PGM1
UR - http://www.scopus.com/inward/record.url?scp=85094171489&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85094171489&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2020.08.003
DO - 10.1016/j.ymgme.2020.08.003
M3 - Article
C2 - 33342467
AN - SCOPUS:85094171489
SN - 1096-7192
VL - 131
SP - 135
EP - 146
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -