Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications.

ABSTRACT:

Objective

Epalrestat, an aldose reductase inhibitor increases phosphomannomutase (PMM) enzyme activity in a PMM2-congenital disorders of glycosylation (CDG) worm model. Epalrestat also decreases sorbitol level in diabetic neuropathy. We evaluated the genetic, biochemical, and clinical characteristics, including the Nijmegen Progression CDG Rating Scale (NPCRS), urine polyol levels and fibroblast glycoproteomics in patients with PMM2-CDG.

Methods

We performed PMM enzyme measurements, multiplexed proteomics, and glycoproteomics in PMM2-deficient fibroblasts before and after epalrestat treatment. Safety and efficacy of 0.8 mg/kg/day oral epalrestat were studied in a child with PMM2-CDG for 12 months.

Results

PMM enzyme activity increased post-epalrestat treatment. Compar

SUBMITTER: Ligezka AN 

PROVIDER: S-EPMC8820356 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature