Research, diagnosis and education in inborn errors of metabolism in Colombia: 20 years' experience from a reference center

Abstract

The use of specialized centers has been the main alternative for an appropriate diagnosis, management and follow up of patients affected by inborn errors of metabolism (IEM). These centers facilitate the training of different professionals, as well as the research at basic, translational and clinical levels. Nevertheless, few reports have described the experience of these centers and their local and/or global impact in the study of IEM. In this paper, we describe the experience of a Colombian reference center for the research, diagnosis, training and education on IEM. During the last 20 years, important advances have been achieved in the clinical knowledge of these disorders, as well as in the local availability of several diagnosis tests. Organic acidurias have been the most frequently detected diseases, followed by aminoacidopathies and peroxisomal disorders. Research efforts have been focused in the production of recombinant proteins in microorganisms towards the development of new enzyme replacement therapies, the design of gene therapy vectors and the use of bioinformatics tools for the understanding of IEM. In addition, this center has participated in the education and training of a large number professionals at different levels, which has contributed to increase the knowledge and divulgation of these disorders along the country. Noteworthy, in close collaboration with patient advocacy groups, we have participated in the discussion and construction of initiatives for the inclusion of diagnosis tests and treatments in the health system.

Keywords: Colombia; Diagnosis; Education; Inborn errors of metabolism; Latin America; Rare diseases; Research; Training.

Fig. 1

Diagnostic tests processed in the reference center. a Number of patient samples analyzed in the last 10 years. b Distribution of requested tests according to clinical suspicion in the last 10 years. AA: aminoacidopathies; OA: organic acidurias; LSD: lysosomal storage disorders; CD: carbohydrate disorders; PD: peroxisomal diseases (Total tests = 9772)

Fig. 2

IEM detected in the reference center. a Diagnosis made according to biochemical-cellular classification of IEM. Data include diagnosis made in the period 2007–2017. b Organic acidurias diagnosed during the last 10 years. These data correspond to cases detected with typical biochemical profiles detected by GC-MS. AA: Aminoacidopathies; LSD: Lysosomal storage disorders; MCD: Multiple carboxylase deficiency; OA: Organic acidurias; PD: Peroxisomal diseases

Fig. 3

Use of bioinformatics tools for the study of IEM. Tertiary structure of human IDS (a) and GALNS (b) enzymes were modeled by protein threading based on the reported structure of other lysosomal enzymes. IDS and GALNS 3D models have been used in phenotype-genotype correlation studies as well as for the design of epitope-specific antibodies. N-glycosylations were modeled by using GlyProt at GLYCOSCIENCES.de server. c Gene enrichment analysis for impaired cellular process in MPS models, identified by a computational systems biology approach