Successful heart transplantation in an infant with phosphoglucomutase 1 deficiency (PGM1-CDG).
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ABSTRACT:
SUBMITTER: Altassan R
PROVIDER: S-EPMC9981415 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
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Successful heart transplantation in an infant with phosphoglucomutase 1 deficiency (PGM1-CDG).
Altassan Ruqaiah R Albert-Brotons Dimpna C DC Alowain Mohammad M Al-Halees Zohair Z Jaeken Jaak J Morava Eva E
JIMD reports 20221122 2
We report successful heart transplantation in a phosphoglucomutase 1 deficient (PGM1-CDG) patient. She presented with facial dysmorphism, bifid uvula and structural heart defects. Newborn screening was positive for classic galactosemia. The patient was on a galactose-free diet for 8 months. Eventually, whole exome sequencing excluded the galactosemia and revealed PGM1-CDG. Oral D-galactose therapy was started. Rapid deterioration of the progressive dilated cardiomyopathy prompted heart transplan ...[more]
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Project description:Phosphoglucomutase 1 (PGM1) deficiency is a rare genetic disorder that affects glycogen metabolism, glycolysis, and protein glycosylation. Previously known as GSD XIV, it was recently reclassified as a congenital disorder of glycosylation, PGM1-CDG. PGM1-CDG usually manifests as a multisystem disease. Most patients present as infants with cleft palate, liver function abnormalities and hypoglycemia, but some patients present in adulthood with isolated muscle involvement. Some patients develop life-threatening cardiomyopathy. Unlike most other CDG, PGM1-CDG has an effective treatment option, d-galactose, which has been shown to improve many of the patients' symptoms. Therefore, early diagnosis and initiation of treatment for PGM1-CDG patients are crucial decisions. In this article, our group of international experts suggests diagnostic, follow-up, and management guidelines for PGM1-CDG. These guidelines are based on the best available evidence-based data and experts' opinions aiming to provide a practical resource for health care providers to facilitate successful diagnosis and optimal management of PGM1-CDG patients.
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Project description:BackgroundCongenital disorders of glycosylation are genetic syndromes that result in impaired glycoprotein production. We evaluated patients who had a novel recessive disorder of glycosylation, with a range of clinical manifestations that included hepatopathy, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, and cardiac arrest.MethodsHomozygosity mapping followed by whole-exome sequencing was used to identify a mutation in the gene for phosphoglucomutase 1 (PGM1) in two siblings. Sequencing identified additional mutations in 15 other families. Phosphoglucomutase 1 enzyme activity was assayed on cell extracts. Analyses of glycosylation efficiency and quantitative studies of sugar metabolites were performed. Galactose supplementation in fibroblast cultures and dietary supplementation in the patients were studied to determine the effect on glycosylation.ResultsPhosphoglucomutase 1 enzyme activity was markedly diminished in all patients. Mass spectrometry of transferrin showed a loss of complete N-glycans and the presence of truncated glycans lacking galactose. Fibroblasts supplemented with galactose showed restoration of protein glycosylation and no evidence of glycogen accumulation. Dietary supplementation with galactose in six patients resulted in changes suggestive of clinical improvement. A new screening test showed good discrimination between patients and controls.ConclusionsPhosphoglucomutase 1 deficiency, previously identified as a glycogenosis, is also a congenital disorder of glycosylation. Supplementation with galactose leads to biochemical improvement in indexes of glycosylation in cells and patients, and supplementation with complex carbohydrates stabilizes blood glucose. A new screening test has been developed but has not yet been validated. (Funded by the Netherlands Organization for Scientific Research and others.).
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