Cardiac Involvement in Pediatric Mucopolysaccharidoses Patients and their Genetic Profile: A Retrospective Single-center Study

Abstract

Mucopolysaccharidoses (MPS) are rare metabolic disorders of monogenic inheritance, with varying degrees of cardiac involvement due to undegraded glycosaminoglycans getting aggregated in the spongiosa of the cardiac valves, the myocardium, and myointima of the coronary arteries. This study is an effort to understand the cardiac involvement and genetic pattern of pediatric MPS patients at a tertiary care center in South India. This descriptive study was done by examining records in our hospital database for MPS patients in the age group of 0–15 years, diagnosed between January 2014 and January 2023. Of these patients, 37 patients with echocardiographic loops available in the hospital system were reevaluated by a single pediatric cardiologist to avoid observer bias. The underlying genetic spectrum was also reviewed. The cohort comprised 67.5% of males and a median age of 9.8 years (interquartile range: 6.5–14.9 years) with a distribution of 37.8% MPS I, 32.4% MPS II, 13.5% MPS IV, and 10.8% MPS VI. Early cardiac involvement in the form of valvar thickening, predominantly left sided (mitral [92%] >aortic [38%]), was seen across all MPS subtypes. We also noted an increased involvement of the tricuspid valve (38%) in our cohort. Moderate–severe valvar involvement was seen in 16% of the cohort, mostly MPS I, II, and VI patients, and more in the second half of the age group (>6 years), suggesting an age-associated worsening of cardiac lesions. Genetic analysis done in 68% of the cohort detected 61% of pathogenic variants, with a predominance of missense mutation (43%). However, no genotype–cardiac phenotype correlation could be ascertained. We identified a high proportion of cardiac abnormalities in our pediatric MPS cohort, which ranged from isolated valvar thickening to a more severe clinical picture, including moderate-to-severe valvular insufficiency and/or stenosis and left ventricular hypertrophy. Cardiac pathology is an early manifestation and a known cause of mortality in many MPS subtypes. Echocardiography is a key diagnostic technique for early detection, careful monitoring, and guidance in the initiation of a timely intervention that will help curb its progression. Hence, the need arises to raise awareness among the primary caretakers of this subset of patients on the need for early cardiac evaluation with a detailed echocardiography.