Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation.

Autor: Zemet R; Dept of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA., Hope KD; Texas Children's Hospital, Houston, TX, USA; Lillie Frank Abercrombie Division of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Edmondson AC; Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Shah R; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA; Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA., Patino M; Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Yesso AM; Dept of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Lillie Frank Abercrombie Division of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Berger JH; Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Sarafoglou K; Divisions of Endocrinology, and Genetics and Metabolism, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA., Larson A; Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA., Lam C; Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, WA, USA; Norcliffe Foundation Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA., Morava E; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA., Scaglia F; Dept of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Joint BCM-CUHK Center of Medical Genetics, Prince of Wales Hospital, Hong Kong SAR, China. Electronic address: fscaglia@bcm.edu.
Jazyk: angličtina
Zdroj: Molecular genetics and metabolism [Mol Genet Metab] 2024 Aug; Vol. 142 (4), pp. 108513. Date of Electronic Publication: 2024 Jun 13.
DOI: 10.1016/j.ymgme.2024.108513
Abstrakt: Introduction: Congenital disorders of glycosylation (CDG) are a continuously expanding group of monogenic disorders that disrupt glycoprotein and glycolipid biosynthesis, leading to multi-systemic manifestations. These disorders are categorized into various groups depending on which part of the glycosylation process is impaired. The cardiac manifestations in CDG can significantly differ, not only across different types but also among individuals with the same genetic cause of CDG. Cardiomyopathy is an important phenotype in CDG. The clinical manifestations and progression of cardiomyopathy in CDG patients have not been well characterized. This study aims to delineate common patterns of cardiomyopathy across a range of genetic causes of CDG and to propose baseline screening and follow-up evaluation for this patient population.
Methods: Patients with molecular confirmation of CDG who were enrolled in the prospective or memorial arms of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study were ascertained for the presence of cardiomyopathy based on a retrospective review of their medical records. All patients were evaluated by clinical geneticists who are members of FCDGC at their respective academic centers. Patients were screened for cardiomyopathy, and detailed data were retrospectively collected. We analyzed their clinical and molecular history, imaging characteristics of cardiac involvement, type of cardiomyopathy, age at initial presentation of cardiomyopathy, additional cardiac features, the treatments administered, and their clinical outcomes.
Results: Of the 305 patients with molecularly confirmed CDG participating in the FCDGC natural history study as of June 2023, 17 individuals, nine females and eight males, were identified with concurrent diagnoses of cardiomyopathy. Most of these patients were diagnosed with PMM2-CDG (n = 10). However, cardiomyopathy was also observed in other diagnoses, including PGM1-CDG (n = 3), ALG3-CDG (n = 1), DPM1-CDG (n = 1), DPAGT1-CDG (n = 1), and SSR4-CDG (n = 1). All PMM2-CDG patients were reported to have hypertrophic cardiomyopathy. Dilated cardiomyopathy was observed in three patients, two with PGM1-CDG and one with ALG3-CDG; left ventricular non-compaction cardiomyopathy was diagnosed in two patients, one with PGM1-CDG and one with DPAGT1-CDG; two patients, one with DPM1-CDG and one with SSR4-CDG, were diagnosed with non-ischemic cardiomyopathy. The estimated median age of diagnosis for cardiomyopathy was 5 months (range: prenatal-27 years). Cardiac improvement was observed in three patients with PMM2-CDG. Five patients showed a progressive course of cardiomyopathy, while the condition remained unchanged in eight individuals. Six patients demonstrated pericardial effusion, with three patients exhibiting cardiac tamponade. One patient with SSR4-CDG has been recently diagnosed with cardiomyopathy; thus, the progression of the disease is yet to be determined. One patient with PGM1-CDG underwent cardiac transplantation. Seven patients were deceased, including five with PMM2-CDG, one with DPAGT1-CDG, and one with ALG3-CDG. Two patients died of cardiac tamponade from pericardial effusion; for the remaining patients, cardiomyopathy was not necessarily the primary cause of death.
Conclusions: In this retrospective study, cardiomyopathy was identified in ∼6% of patients with CDG. Notably, the majority, including all those with PMM2-CDG, exhibited hypertrophic cardiomyopathy. Some cases did not show progression, yet pericardial effusions were commonly observed, especially in PMM2-CDG patients, occasionally escalating to life-threatening cardiac tamponade. It is recommended that clinicians managing CDG patients, particularly those with PMM2-CDG and PGM1-CDG, be vigilant of the cardiomyopathy risk and risk for potentially life-threatening pericardial effusions. Cardiac surveillance, including an echocardiogram and EKG, should be conducted at the time of diagnosis, annually throughout the first 5 years, followed by check-ups every 2-3 years if no concerns arise until adulthood. Subsequently, routine cardiac examinations every five years are advisable. Additionally, patients with diagnosed cardiomyopathy should receive ongoing cardiac care to ensure the effective management and monitoring of their condition. A prospective study will be required to determine the true prevalence of cardiomyopathy in CDG.
Competing Interests: Declaration of competing interest The authors report no conflict of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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