ENIntractable & Rare Diseases Research | Clinical Significance of Early Screening for Respiratory and Cardiac Complications in MPS IVA
Date: April 05, 2025
Classification: Frontiers
Recommend:
This study highlights the importance of early screening for cardiac and respiratory complications in pediatric mucopolysaccharidosis IVA (MPS IVA) patients. Whole exome sequencing (WES) eventually led to the diagnosis, but the patient still died from acute respiratory failure and heart failure due to insufficient early screening and ineffective treatment, underscoring the need for improved diagnostic workflows and enhanced multi-system evaluations.
Literature Overview
This article titled 'Early screening for respiratory and cardiac complications in pediatric mucopolysaccharidosis IVA: Insights from a case' was published in the journal Intractable & Rare Diseases Research. It reviews and summarizes the clinical features and genetic mutation analysis of a single 11-year-old male patient with mucopolysaccharidosis IVA (MPS IVA). The article indicates that due to diverse clinical manifestations and lack of early screening, the disease is often misdiagnosed or diagnosed with delay, affecting treatment timing. MPS IVA is an autosomal recessive disorder caused by mutations in the GALNS gene, leading to deficiency of N-acetylgalactosamine-6-sulfatase, which causes multi-system involvement, significantly affecting growth and development and increasing mortality risk.
Background Information
Mucopolysaccharidosis type IVA (Morquio A syndrome) is a rare lysosomal storage disorder primarily caused by mutations in the GALNS gene that result in loss of enzyme function, leading to abnormal accumulation of keratan sulfate and chondroitin sulfate. Clinical features include skeletal deformities, joint hypermobility, coarse facial features, and cardiorespiratory dysfunction. Cardiac involvement, mainly manifested as valvular disease, pulmonary hypertension, and heart failure, is a major cause of disease-related mortality. Due to nonspecific symptoms and multi-system involvement, diagnosis is often delayed, with an average delay of 9.42 months and an average of 4.56 misdiagnoses. Current diagnostic methods include enzyme activity testing and genetic sequencing, with whole exome sequencing (WES) shown to significantly improve early diagnosis. Studies have also demonstrated that early enzyme replacement therapy can effectively improve cardiac function, and respiratory interventions can significantly reduce mortality. Therefore, optimizing the diagnostic process, improving screening efficiency, and performing early cardiorespiratory assessment after diagnosis are important research directions.
Research Methods and Findings
This study is a single-center case report involving a male patient aged 11 years and 6 months, who presented with chronic growth delay and declining physical activity. In 2017, the patient underwent multiple lysosomal enzyme activity tests, which showed no abnormalities. Without further genetic screening, diagnosis was delayed until 2025, when whole exome sequencing (WES) finally confirmed mucopolysaccharidosis IVA (MPS IVA). Following diagnosis, echocardiography and X-ray imaging revealed left atrial and ventricular dilatation, mitral regurgitation, and pulmonary hypertension. The patient rapidly progressed to acute respiratory failure and eventually died of cardiopulmonary arrest.
Key Conclusions and Insights
Significance and Future Directions
This case emphasizes the necessity of integrating genetic testing into the diagnostic workflow for mucopolysaccharidoses. Future studies should focus on establishing standardized screening pathways and combining enzyme replacement therapy with respiratory support to improve outcomes. In addition, building genotype-phenotype databases will enhance diagnostic accuracy and treatment decision-making.
Conclusion
This study, by reviewing a case of delayed diagnosis of MPS IVA, reveals the critical role of early screening in rare disease management. The patient presented with chronic growth delay and declining mobility but was not diagnosed in a timely manner due to initial partial enzyme activity testing, leading to irreversible progression of cardiorespiratory complications. By the time of genetic confirmation, the condition had severely deteriorated. Therefore, it is recommended that enzyme activity and genetic testing be integrated early in suspected cases to improve diagnostic efficiency. Additionally, prompt cardiopulmonary assessment post-diagnosis is essential to formulate intervention strategies. Widespread implementation of newborn screening, optimized genetic diagnostic pathways, and multidisciplinary care may significantly improve patient outcomes. This study further supports the importance of integrating genomics with clinical evaluation in pediatric rare disease diagnostics, offering practical guidance for clinicians.
