A new D-galactose treatment monitoring index for PGM1-CDG

Ester Perales-Clemente, Kristen Liedtke, April Studinski, Silvia Radenkovic, Dimitar Gavrilov, Devin Oglesbee, Dietrich Matern, Piero Rinaldo, Silvia Tortorelli, Eva Morava, Kimiyo Raymond

Research output: Contribution to journalArticlepeer-review


Phosphoglucomutase 1 (PGM1) catalyzes the interconversion of glucose-6-phosphate to glucose-1-phosphate and is a key enzyme of glycolysis, glycogenesis, and glycogenolysis. PGM1 deficiency (OMIM: 614921) was initially defined as a glycogen storage disorder (type XIV), and later re-classified as a PGM1-congenital disorder of glycosylation (PGM1-CDG). Serum transferrin (Tf) glycan isoform analysis by liquid chromatography-mass spectrometry (LC-MS) is used as a primary diagnostic screen tool, and reveals a very unique CDG profile described as a mixture of CDG-type I and CDG-type II patterns. Oral d-galactose supplementation shows significant clinical and metabolic improvements, which are indicated by the Tf glycan isoform normalization over time in patients with PGM1-CDG. Thus, there is a need for biomarkers to guide d-galactose dosage in patients in order to maintain effective and safe drug levels. Here, we present a simplified algorithm called PGM1-CDG Treatment Monitoring Index (PGM1-TMI) for assessing the response of PGM1-CDG patients to d-galactose supplementation. For our single-center cohort of 16 PGM1-CDG patients, the Tf glycan profile analysis provided the biochemical diagnosis in all of them. In addition, the PGM1-TMI was reduced in PGM1-CDG patients under d-galactose supplementation as compared with their corresponding values before treatment, indicating that glycosylation proceeds towards normalization. PGM1-TMI allows tracking Tf glycan isoform normalization over time when the patients are on d-galactose supplementation.

Original languageEnglish (US)
Pages (from-to)1263-1271
Number of pages9
JournalJournal of inherited metabolic disease
Issue number5
StatePublished - Sep 2021


  • PGM1-CDG treatment monitoring index (PGM1-TMI)
  • congenital disorder of glycosylation
  • liquid chromatography-mass spectrometry
  • oral d-galactose supplementation
  • phosphoglucomutase 1
  • serum transferrin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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