Abstract
Glycosylphosphatidylinositol anchoring disorders (GPI-ADs) are a subgroup of congenital disorders of glycosylation. GPI biosynthesis requires proteins encoded by over 30 genes of which 24 genes are linked to neurodevelopmental disorders. Patients, especially those with PIGA-encephalopathy, have a high risk of premature mortality which sometimes is attributed to cardiomyopathy. We aimed to explore the occurrence of cardiomyopathy among patients with GPI-ADs and to raise awareness about this potentially lethal feature. Unpublished patients with genetically proven GPI-ADs and cardiomyopathy were identified through an international collaboration and recruited through the respective clinicians. We also reviewed the literature for published patients with cardiomyopathy and GPI-AD and contacted the corresponding authors for additional information. We identified four novel and unrelated patients with GPI-AD and cardiomyopathy. Cardiomyopathy was diagnosed before adulthood and was the cause of early demise in two patients. Only one patients underwent cardiac workup after being diagnosed with a GPI-AD. All were diagnosed with PIGA-encephalopathy and three had a disease-causing variant at the same residue. The literature reports five additional children with GPI-AD related cardiomyopathy, three of which died before adulthood. We have shown that patients with GPI-ADs are at risk of developing cardiomyopathy and that regular cardiac workup with echocardiography is necessary.
Original language | English |
---|---|
Journal | Clinical Genetics |
Volume | 104 |
Issue number | 5 |
Pages (from-to) | 598-603 |
ISSN | 0009-9163 |
DOIs | |
Publication status | Published - Nov 2023 |
Bibliographical note
Publisher Copyright:© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.
Keywords
- cardiomyopathy
- genetics
- glycosylphosphatidylinositol biosynthesis defects
- GPI
- GPIAD
- heart
- mortality
- PIGA
- Humans
- Adult
- Brain Diseases
- Cardiomyopathies/diagnosis
- Glycosylphosphatidylinositols/genetics
- Child