Phenotype-Genotype Correlation in Morquio A Syndrome: Protocol for a Meta-Analysis.

Background: Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome, is a rare lysosomal storage disease characterized by autosomal recessive inheritance of mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. This leads to a deficiency of the GALNS enzyme, causing the accumulation of glycosaminoglycans in tissues. Morquio A syndrome primarily affects the skeletal system and joints but can also impact various organs, resulting in symptoms such as hearing and vision loss, respiratory issues, spinal cord compression, heart diseases, and hepatomegaly. The genotype-phenotype relationship is diverse, with studies highlighting variants associated with classic, nonclassic, or intermediate phenotypes. Understanding these genetic factors is crucial for predicting disease prognosis and tailoring effective treatment strategies for individuals with Morquio A syndrome.

Objective: The aim of this meta-analysis is to comprehend the relationship between the severity of the phenotype and the genotype of patients with MPS IVA, considering factors such as the type of variant and its location in the different domains of the protein.

Methods: This meta-analysis will include articles featuring participants of all genders and age groups who have a molecular diagnosis of MPS IVA and a description of the phenotype. Literature published in English, Spanish, and Portuguese will be considered. Exclusion criteria will encompass studies lacking full-text availability and those involving patients with an MPS IVA diagnosis but without phenotype information. The databases to be searched include PubMed, MEDLINE, ScienceDirect, and Scopus. The screening of literature, paper selection, and data extraction will involve 2 independent reviewers, who will conduct the process blindly. In the event of disagreements between the 2 reviewers at any stage, resolution will be sought through discussion or with the involvement of an additional reviewer. The final selection of manuscripts will be based on consensus. The results of the review will be presented using descriptive statistics, and the information will be organized in either diagrammatic or tabular formats, following the guidelines provided by the Joanna Briggs Institute. Genotype-phenotype relationships will be analyzed using IBM SPSS Statistics, using chi-square tests, Fisher exact tests, and regression analysis to interpret the data.

Results: A literature search conducted in January 2024 produced 760 results. The review is expected to be completed by the end of 2024.

Conclusions: This meta-analysis will gather and analyze information on the phenotype-genotype relationship in patients diagnosed with MPS IVA. The data collection and resulting analyses will make a substantial contribution to understanding the underlying mechanism of the disease, enabling the prediction of the syndrome's progression and severity.

International registered report identifier (irrid): DERR1-10.2196/56649.