Mol Genet Metab. 2025 Nov 27:109687. doi: 10.1016/j.ymgme.2025.109687. Online ahead of print.
ABSTRACT
BACKGROUND: Mucopolysaccharidoses (MPS) are lysosomal storage disorders characterised by glycosaminoglycan (GAG) accumulation, leading to progressive multisystem disease. Cardiovascular complications, including arterial wall stiffness, and valvular dysfunction, are major causes of morbidity and mortality. Conventional cardiovascular risk tools are unreliable in MPS, and the role of vascular imaging remains underdefined.
AIM: This systematic review evaluated vascular complications in paediatric and adult MPS patients, focusing on carotid intimal-media thickness (CIMT) and functional vascular parameters (e.g. carotid cross-sectional compliance (cCSC), carotid incremental elastic modulus (cIEM), carotid cross-sectional distensibility (cCSD)), to assess their utility for cardiovascular risk stratification.
METHODS: A systematic search of MEDLINE, EMBASE, and Cochrane Library was conducted (inception-July 2025). Eligible studies reported vascular outcomes in MPS types I, II, III, IV, VI, or VII using imaging or functional measures. Risk of bias was assessed using ROBINS-I for observational studies and RoB 2.0 for the single randomised trial.
RESULTS: Eight studies comprising 224 patients were included. CIMT was consistently increased across subtypes, with adult values frequently observed in childhood, indicating accelerated vascular pathology. Patients demonstrated reduced arterial compliance, increased arterial stiffness, and a high prevalence of mitral and aortic valvular disease. Enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT) showed partial attenuation of vascular pathology.
CONCLUSION: CIMT and vascular stiffness are sensitive markers of subclinical vasculopathy in MPS where conventional cardiovascular risk tools may remain unreliable. Standardised vascular imaging and biomarker development are needed to improve risk stratification and long-term outcomes (particularly in adults).
PMID:41320576 | DOI:10.1016/j.ymgme.2025.109687