Phosphoglucomutase-1 deficiency: Early presentation, metabolic management and detection in neonatal blood spots

Federica Conte, Eva Morava, Nurulamin Abu Bakar, Saskia B. Wortmann, Anne Jonge Poerink, Stephanie Grunewald, Ellen Crushell, Lihadh Al-Gazali, Maaike C. de Vries, Lars Mørkrid, Jozef Hertecant, Katja S. Brocke Holmefjord, David Kronn, Annette Feigenbaum, Ralph Fingerhut, Sunnie Y. Wong, Monique van Scherpenzeel, Nicol C. Voermans, Dirk J. Lefeber

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)135-146
Number of pages12
JournalMolecular Genetics and Metabolism
Issue number1-2
Publication statusPublished - Sept 1 2020


  • Congenital disorder of glycosylation
  • Dilated cardiomyopathy
  • Exercise intolerance
  • Galactose
  • Hypoglycemia
  • PGM1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology


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