Twenty years of Colombian experience with enzymatic screening in patients with features of mucopolysaccharidosis

Abstract

Mucopolysaccharidoses (MPSs) are a group of genetic alterations whose effect is the progressive intralysosomal accumulation of glycosaminoglycans. Affected individuals are deficient in one or more lysosomal enzymes which, depending on the MPS, may cause coarse facial features, short stature, multiple skeletal dysplasia, joint stiffness, or developmental delay. Their diagnosis is mostly performed late or incorrectly, and it represents a challenge since it requires specialized tests only performed in major cities. This makes it difficult for patients to have access to physicians since their geographical location is distant and therefore, the use of samples collected in solid‐phase represents an advantage for the study of high‐risk populations. In addition, epidemiological information about rare diseases, especially in Latin America, is scarce or inconsistent. Our aim was to report the experience of 20 years of selective screening by assessing enzyme activity and reporting incidence values of MPS in Colombia. This study validated a group of fluorometric endpoint techniques in 8239 patients. The samples were dried blood spots (DBS) collected on filter paper and leukocyte extracts. Reference values in the Colombian population for α‐ l ‐iduronidase, iduronate 2‐sulfatase, α‐ N ‐acetylglucosaminidase, N ‐acetylglucosamine‐6‐sulfate sulfatase, β‐galactosidase, arylsulfatase B, and β‐glucuronidase were established in leukocyte extracts, and patients reference ranges were updated in the case of DBS samples. Incidence values were calculated for each MPS and the distribution of cases across the country is also shown. This study offers very useful information for the health system, the scientific community, and it facilitates the diagnosis of these disorders. This is indispensable when seeking to develop new diagnostic or treatment approaches for patients.

Current Status of Newborn Bloodspot Screening Worldwide 2024: A Comprehensive Review of Recent Activities (2020–2023)

“…Colombia —A 2019 law formalized an expansion of the national NBS program from CH to seven conditions and included EHDI and vision screening [ 1182 , 1183 , 1184 , 1185 ]. Efforts to continue expanding DBS screening have included developing MS/MS cutoff values and reviewing experiences and policy issues with MPS and other LSDs [ 1186 , 1187 , 1188 , 1189 ]. Continued interest in CCHD screening has included cost-effectiveness studies as well as a 14-site collaboration with the Nicklaus Children’s Hospital (Miami, Florida USA) [ 1190 , 1191 ].…”

“…Colombia-A 2019 law formalized an expansion of the national NBS program from CH to seven conditions and included EHDI and vision screening [1182][1183][1184][1185]. Efforts to continue expanding DBS screening have included developing MS/MS cutoff values and reviewing experiences and policy issues with MPS and other LSDs [1186][1187][1188][1189].…”

Evidence of epigenetic landscape shifts in mucopolysaccharidosis IIIB and IVA

“…Conversely, MPS IIIB arises from gene variants in the N-acetylglucosaminidase ( NAGLU ) gene that leads mainly to neurodegeneration due to the lysosomal storage of heparan sulfate. In Colombia, MPS IVA stands as the most prevalent MPS subtype, with a combined prevalence of 1.98 and approximately 200 diagnosed patients 20 – 22 , while MPS IIIB ranks as the third most common, with 10.8% of the diagnosed patients and an estimated incidence of 0.36 affected individuals per 100,000 live births 22 . During the last few years, we have studied the cellular and molecular mechanisms of MPS IVA and MPS IIIB 17 , 23 , 24 , testing the potential of different therapeutic alternatives including recombinant enzymes 25 – 29 , gene therapy 30 – 34 , and pharmacological chaperones 35 – 37 .…”

Identification of Orthosteric and Allosteric Pharmacological Chaperones for Mucopolysaccharidosis Type IIIB

“…[8][9] For MPS IIIB, 256 mutations have been identified in the NAGLU gene, from which about 70 % are missense (The Human Gene Mutation Database, accessed February 2023, and [8][9] ). In Colombia, a recent report by Uribe-Ardila, et al [10] showed that MPS IIIB is the third more common MPS, with a 10.8 % of the MPS diagnosed patients and an estimated incidence of 0.36 affected individuals per 100,000 live births.…”