α-mannosidosis diagnosis in Brazilian patients with MPS-like symptoms

Author(s)

Marins, Maryana ; Curiati, Marco Antonio ; Gomes, Caio Perez ; Martin, Renan Paulo ; Nicolicht-Amorim, Priscila ; Yamamoto, Joyce Umbelino da Silva ; D'Almeida, Vania ; Martins, Ana Maria ; Pesquero, Joao Bosco

• Document type: Journal article
• Source: ORPHANET JOURNAL OF RARE DISEASES; v. 19, n. 1, p. 10-pg., 2024-11-26.

Abstract

Background alpha-mannosidosis is an inborn error of metabolism caused by the deficiency of the lysosomal enzyme alpha-mannosidase, which is encoded by the MAN2B1 gene and inherited in an autosomal recessive manner. The impairment of affected individuals is multisystemic and very similar to the observed in some mucopolysaccharidosis (MPS) patients. The aim of this study was to search for alpha-mannosidosis cases in individuals with clinical suspicion of MPS without a confirmed diagnosis. Biochemical and molecular analysis were standardized by our group for this study. Two hundred and fifty samples from patients with clinical suspicion of MPS, but with inconclusive MPS biochemical and/or molecular analysis, were screened for alpha-mannosidase activity. Subsequently the MAN2B1 gene was sequenced in samples from 53 patients by the Sanger method.ResultsThe measurement of enzymatic activity detected fifty-three samples with abnormal results, suggesting alpha-mannosidosis. Molecular analysis confirmed three affected families, which presented the nonsense variant p.Ser899Ter. This variant generates a premature stop codon in exon 22, resulting in a truncated protein with no residual enzymatic activity.ConclusionIn conclusion, this work brings data for the beginning of a genetic characterization of alpha-mannosidosis in the Brazilian population. It also shows that alpha-mannosidosis cases may be underdiagnosed due to the clinical similarity to MPS and the lack of information about this ultra-rare disease. Based on our data, we strongly recommend to all screening centers to consider alpha-mannosidosis testing together with screening for MPS as a tool for diagnosis to MPS-like phenotype individuals, since the phenotype similarity between these diseases poses a significant challenge for clinicians worldwide and often leads to the failure of the correct clinical diagnosis and treatment. (AU)

• FAPESP's process: 20/14635-1 - Modeling of monogenic diseases for physiopathological studies and pharmacological tests using specialized cells derived from iPSCs
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants