期刊
JOURNAL OF INHERITED METABOLIC DISEASE
卷 44, 期 5, 页码 1263-1271出版社
WILEY
DOI: 10.1002/jimd.12406
关键词
congenital disorder of glycosylation; liquid chromatography-mass spectrometry; oral d-galactose supplementation; PGM1-CDG treatment monitoring index (PGM1-TMI); phosphoglucomutase 1; serum transferrin
资金
- National Institute of Health NINDS/NCATS Frontiers in Congenital Disorders of Glycosylation Grant [1U54NS115198-01]
- Rare Disorders Consortium Disease Network
- T. Denny Sanford Professorship Fund
PGM1 deficiency, initially defined as a glycogen storage disorder, was later re-classified as PGM1-congenital disorder of glycosylation. Analysis of serum transferrin glycan isoforms is used as a primary diagnostic tool. Oral d-galactose supplementation has been shown to significantly improve clinical and metabolic outcomes in PGM1-CDG patients.
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.
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