Lysosomal storage diseases (LSDs) are a group of about 50 inborn errors of metabolism characterized by the lysosomal accumulation of partially or non-degraded molecules due to mutations in proteins involved in the degradation of macromolecules, transport, lysosomal biogenesis or modulators of lysosomal environment. Significant advances have been achieved in the diagnosis, management, and treatment of LSDs patients. In terms of approved therapies, these include enzyme replacement therapy (ERT), substrate reduction therapy, hematopoietic stem cell transplantation, and pharmacological chaperone therapy. In this review, we summarize the Colombian experience in LSDs thorough the evidence published. We identified 113 articles published between 1995 and 2019 that included Colombian researchers or physicians, and which were mainly focused in Mucopolysaccharidoses, Pompe disease, Gaucher disease, Fabry disease, and Tay-Sachs and Sandhoff diseases. Most of these articles focused on basic research, clinical cases, and mutation reports. Noteworthy, implementation of the enzyme assay in dried blood samples, led to a 5-fold increase in the identification of LSD patients, suggesting that these disorders still remain undiagnosed in the country. We consider that the information presented in this review will contribute to the knowledge of a broad spectrum of LSDs in Colombia and will also contribute to the development of public policies and the identification of research opportunities.
La Enfermedad de Krabbe (EK), es un desorden del metabolismo de esfingolípidos de herencia autosómica recesiva causada por la deficiencia de β- galactosilceramidasa (β-Galsil) (E.C. 3.2.1.46), defecto enzimático que causa un cuadro neurodegenerativo, hipertonía muscular y espasticidad, convulsiones, pérdida de la audición y en un 85% de los casos la muerte temprana, entre otros hallazgos.La incidencia de la EK documentada para Estados Unidos y Europa es de 1:100.000 recién nacidos, pero estudios recientes han demostrado valores mayores de 1:22.000 aproximadamente en New York. En América Latina los informes son escasos, con reportes de tamizaje de alto riesgo en Brasil y casos aislados en México, ofreciendo un panorama de subdiagnóstico importante, situación a la que no es ajena Colombia, donde no hay en la literatura referentes a la enfermedad.Se presenta entonces a la comunidad científica, un estudio de valores de actividad y de referencia para la enzima β-Galactosilceramidasa leucocitaria, a partir de 259 muestras de 110 individuos sanos y 149 pacientes con compromiso neurodegenerativo (CND). La valoración enzimática involucró dos métodos (Colorimétrico y Fluorométrico) de punto final que permitieron establecer un rango de referencia para β-Galsil en técnica Colorimétrica: 2,04 -14,93 nmol/mgprot/h y en técnica fluorométrica: 0,3 – 4,21 nmol/mgprot/h. El estudio de tamizaje permitió identificar un paciente afectado con enfermedad de Krabbe quien presentó valores de actividad expresados en nmol/mgprot/h de 1,85 y 0,034, en forma correspondiente para las técnicas antes descritas. Un hallazgo final que permite validar los dos métodos estandarizados para el diagnóstico de la enfermedad y establecer valores de referencia en población colombiana.
RESUMENLa deficiencia de la Glucosa 6 Fosfato Deshidrogenasa es un desorden hereditario del metabolismo ligado al cromosoma X, considerada como la enfermedad metabólica de mayor frecuencia a nivel mundial con más de 400 millones de individuos afectados, es la causa más común de anemia hemolítica no autoinmune de origen metabólico. La prevalencia calculada para Colombia según la organización mundial de la salud se encuentra entre 3 -7%, pero los reportes de estudios poblacionales son escasos, creando la necesidad de incluir esta deficiencia en un programa de tamizaje neonatal, más cuando aproximadamente un 11 % de la población es afrodescendiente, que sin contar con el mestizaje, puede ofrecer una frecuencia mayor de la deficiencia en ciertas regiones del país.El presente estudio brinda entonces, una panorámica general de la prevalencia de esta enzimopatía eritrocitaria, en población con anemia hemolítica crónica o episódica de naturaleza no inmune, procedentes de diferentes lugares del territorio nacional. Comprende la valoración de 3837 muestras durante el periodo 1998 al 2016, un total de 1801 controles y 2036 individuos (982 hombres/1054 mujeres, Rango de edad: 1 semana a 91 años) con hallazgos sugerentes de esta condición metabólica.Los resultados encontrados, ofrecen una prevalencia del 7 % de la deficiencia con grados variables de actividad residual. El rango general de los grupos control osciló entre 3,31 -9,98 UI/gr HB, contrastante contra el grupo de afectados (n=144) que ofreció un valor de 0,0 -2,97, el 67 % (n=96) correspondiente a varones afectados. Estos hallazgos evidencian la importancia de incluir dentro de un programa de detección neonatal, esta enzimopatía eritrocitaria.Palabras claves: Anemia hemolítica; Glucosa-6-fosfato deshidrogenasa; Estrés oxidativo eritrocitario; Enzimopatías eritrocitarias. 8Uribe A. GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY IN COLOMBIA: MEMORIES OF TWENTY-TWO YEARS OF HIGH RISK SCREENING ABSTRACTDeficiency of Glucose-6 -Phosphate Dehydrogenase is an inherited disorder of X-linked metabolism, as the metabolic disease of the world's largest frequency with more than 400 million affected individuals, is the most common cause of non-autoimmune hemolytic anemia of metabolic origin. The prevalence calculated for Colombia according to the world health organization is between 3 and 7%, but the reports of population studies are scarce, creating the need to include this deficiency in a neonatal screening program, closer to 11% population is Afro-descendant that without the miscegenation, can offer a greater frequency of deficiency in certain regions of the country.The present study provides an overview of the prevalence of erythrocyte enzyme disease in the population with chronic or episodic hemolytic anemia of non-immune nature from different parts of the national territory. It comprises the evaluation of 3837 samples during the period 1998 to 2016, a total of 1801 controls and 2036 individuals (982 men / 1054 women, age range: 1 week to 91 years) with suggestive findings of...
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.
Fabry disease is a metabolic alteration linked to an enzymatic deficiency of Alpha-Galactosidase A, this disorder compromises the sphingolipid metabolism, leading to an accumulation of lysosomal globotriaosylceramide and is inherited in an X-linked recessive way. The diagnostic of this disease, in general, requires the confirmation of below-normal levels of Alpha-Galactosidase A obtained from dried blood spot (DBS) samples, followed by an assessment of the enzyme in leukocytes. We aimed to report the Alpha-Galactosidase A values obtained in Colombian males with end-stage renal disease (ESRD) screened using dried blood spot samples during ten years. This screening was performed with samples sent to the analysis center from 6156 patients between 2006-2016. All patients with low levels in enzyme activity (compared to the control population) were sent to confirmation through enzyme analysis in isolated leukocytes. 26 males (0.42%) with low levels of Alpha-Galactosidase A were identified (Range 0.0 -1.14 nmol/ ml/hour, cut-off: 1.15), 22 patients were subsequently measured in isolated leukocytes having a confirmation of Fabry disease in 5 patients (0.08% of total male population) (Range: 0.3 -4.7 nmol/mg prot/h). These results are similar to those reported in studies with comparable characteristics being this the first reporting frequency of Fabry disease among Colombian males with end-stage renal disease.
Sanfilippo B is a lysosomal disorder characterized by the pathological accumulation of heparan sulfate. It is caused by mutations in the NAGLU gene that codes for the alpha-N-acetylglucosaminidase enzyme. The objective of this study was to determine the reference values and frequency of Sanfilippo B in Colombia through an enzyme analysis of leukocytes extracts. We aim to inform the community and the health system so that they can work in a preventive way, providing an early diagnosis of patients and thus providing an appropriate management of the symptoms. We carried out an endpoint assay that indirectly quantifies NAGLU activity through the cleavage of 4-methylumbelliferone from the 4-methylumbelliferyl-2-acetamido-2-deoxy-α-D-glucopyranoside substrate. The activity of 463 healthy volunteers (Range: 0.6 -4 nmol/mg/h , Median: 1.69 +/-0.73 ) as well as 462 patients referred for clinical suspicion, was calculated. From the last group, 7 cases turned out to be positive (Range: 0 -0.24 nmol/mg/h , Median: 0.13 +/-0.09 ). The cut-off point according to ROC analysis between affected patients and controls was 0.42 nmol/mg/h. To our knowledge, this study is the first in Colombia where an estimated frequency of Sanfilippo type B is calculated by providing enzyme activity ranges and a cut-off point.
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