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 - Funding Information:
This study is supported by the Prinses Beatrix Spierfonds (W.OR15 to Conte F.), the Netherlands Organization for Scientific Research (ZONMW Med. Inv. grant 40-00506-98-9001 and VIDI grant 91713359 to Lefeber D.J.), the Hayward Trustees and LaCATS. This work has been also been part of the U54 (U54 FP00100950 grant, Morava E.). The authors would like to thank Dr. Frank Bowling (Royal Melbourne hospital, AU) for the initial clinical recognition of patient 2, and Dr. Daisy Rymen (Abteilung Stoffwechselkrankheiten Assistenzärztin, Universitäts-Kinderspital Zurich, CH) for the extra clinical details about the not previously unpublished patient described in her conference poster presented at the 2012 SSIEM Conference (Birmingham, UK) [32].
Funding Information:
This study is supported by the Prinses Beatrix Spierfonds (W.OR15 to Conte F.), the Netherlands Organization for Scientific Research (ZONMW Med. Inv. grant 40-00506-98-900 1 and VIDI grant 91713359 to Lefeber D.J.), the Hayward Trustees and LaCATS . This work has been also been part of the U54 (U54 FP00100950 grant, Morava E.). The authors would like to thank Dr. Frank Bowling (Royal Melbourne hospital, AU) for the initial clinical recognition of patient 2, and Dr. Daisy Rymen (Abteilung Stoffwechselkrankheiten Assistenzärztin, Universitäts-Kinderspital Zurich, CH) for the extra clinical details about the not previously unpublished patient described in her conference poster presented at the 2012 SSIEM Conference (Birmingham, UK) [ 32 ].
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
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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 -