Biochemical diagnosis of mucopolysaccharidosis in a Mexican reference center

Sandra Del Carmen Mendoza-Ruvalcaba,José Elías García-Ortiz,Jesús Alejandro Juárez-Osuna,Aniel Jessica Leticia Brambila-Tapia,Thiago Donizete Da Silva-José

doi:10.1590/1678-4685-gmb-2018-0347

Sandra Del Carmen Mendoza-Ruvalcaba, José Elías García-Ortiz + Show 3 more

Open Access

https://doi.org/10.1590/1678-4685-gmb-2018-0347

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Abstract

Mucopolysaccharidoses (MPS) are a group of genetic disorders, each resulting from the deficiency of one of the lysosomal enzymes that catabolizes mucopolysaccharides. For the accurate diagnosis of the disease, the quantification of a specific enzymatic activity is needed. In the present study, we analyzed seven MPS over several periods of time ranging from 2 to 5 years in a reference center in Mexico. During this time, a total of 761 samples belonging to 505 individuals with suspected MPS were analyzed. A total of 198 (26.01%) positive results were found. Among these, MPS IVA accounted for the highest frequency of positive results (49.10%), followed by MPS III (17.69%, IIIA: 11.80% and IIIB: 5.89%). Adjusting for the number of births per year, the estimated incidence per 100,000 births for MPS analyzed were as follows: MPS I: 0.19, MPS II: 0.15, MPS IIIA: 0.26, MPS IIIB: 0.13, MPS IVA: 1.10, MPS VI: 0.17 and MPS VII: 0.23, and the combined estimated incidence of MPS was 2.23 per 100,000 births; however, this incidence seems to be highly underestimated when compared with the results of newborn screenings.

Highlights

Mucopolysaccharidoses (MPS) are a heterogeneous group of rare inherited disorders, each caused by a deficiency of one of the lysosomal enzymes that catabolizes complex carbohydrates known as mucopolysaccharides or glycosaminoglycans (GAG)
We present the initial results from a reference center in Mexico that evaluated the enzymatic activities of 7 different types of MPS (I, II, IIIA, IIIB, IVA, VI, and VII) over a period of 5 years
The residual activities of each of the enzymes (MPS I, MPS II, MPS IIIA, MPS IIIB, MPS IVA, MPS VI and MPS VII) were measured using the fluorogenic substrate 4-methylumbelliferyl (4MU) as follows: the detection of the enzymatic activity in MPS I was performed according to the method of Ou et al (2014), with the substrate 4MU-a-L-iduronide (Glycosynthâ, code 44076); Moscerdam Substratesâ were used for the analysis of MPS II, with the substrate 4MU-alpha-L-iduronide-2-sulphate (Voznyi et al, 2001); MPS IIIA, with the substrate 4MU-alpha-N-sulpho-D-glucosaminide (Karpova et al, 1996); MPS IIIB, with the substrate 4MU-alpha-N-acetyl-glucosaminide (Marsh and Fensom, 1985); and MPS IVA, with the substrate 4MU–Beta-D-galactoside6-sulphate (Van Diggelen et al, 1990)

Summary

Introduction

Mucopolysaccharidoses (MPS) are a heterogeneous group of rare inherited disorders, each caused by a deficiency of one of the lysosomal enzymes that catabolizes complex carbohydrates known as mucopolysaccharides or glycosaminoglycans (GAG). MPS are classified into seven different types (I, II, III, IV, VI, VII and IX), and MPS III and IV are further classified into four and two subtypes, respectively. In addition to the attenuated and severe phenotypes observed with almost all of the MPS types, the diagnosis of MPS is based on the enzymatic activities of leukocytes, fibroblasts or plasma (Cimaz and La Torre, 2014). We present the initial results from a reference center in Mexico that evaluated the enzymatic activities of 7 different types of MPS (I, II, IIIA, IIIB, IVA, VI, and VII) over a period of 5 years (from 2012-2017)

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Conclusion