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Abstract Mucopolysaccharidoses are lysosomal storage diseases characterized by the excessive accumulation of glycosaminoglycan sulfate in organs and tissues. To determine the population allelic frequency of the MPS complex variants in a population without clinical and molecular diagnosis of MPS. An observational descriptive study was carried out where the allelic frequency of variants presents in the IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, GLB1, ARSB, GUSB, HYAL1 genes was determined by means of the sequencing of 320 exomes from patients without a clinical diagnosis of MPS; the results were tabulated, and allelic frequency formulas were used to determine the values associated with each of the genes. 509 alleles associated with the MPS complex were reported, of which 262 have not been previously reported. Genes with the most frequent allelic presence were IDUA, GLB1 and GALNS, involved in MPS I and MPS IV A / B. The total frequencies ranged between 0.00393 (2 alleles) and 0.47937 (248 alleles). These studies make it possible to determine polymorphisms that circulate in the country, present in patients not affected with MPS, allowing to expand the knowledge about the characteristics of the alleles that are present in affected patients.

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La hemimelia tibial se puede presentar en una gran variedad de espectros, desde la hipoplasia tibial hasta la ausencia completa de la tibia con o sin compromiso adjunto cuadricipital, ligamentario, patelar, fibular y/o femoral; esto ha dado lugar a múltiples clasificaciones con implicaciones anatómicas y terapéuticas. Esta enfermedad se ha descrito desde 1841, sin embargo, es la deficiencia más rara en las extremidades inferiores, siendo la más común la deficiencia fibular. Presentamos un paciente con diagnóstico antenatal de pie equino varo bilateral, agenesia de la tibia izquierda y comunicación aurículo ventricular (CIA) con cariotipo normal. Al nacer presenta fascies normales. Se confirma con radiografías la ausencia del tercer rayo de la mano izquierda y la ausencia de la tibia izquierda con ensanchamiento del peroné, tipo 5C en la clasificación de Paley, y pie equino varo aducto bilateral. Nivel de Evidencia: IV

Tibial hemimelia is a broad spectrum disorder, from tibial hypoplasia to complete absence of the tibia with or without quadricipital, ligament, patellar, fibular and / or femoral attachment. This has led to multiple classifications, with their anatomical and therapeutic implications. Although this disorder has been described since 1841, it is the rarest deficiency in the lower extremities, with the most common being fibular deficiency. The case is presented on a patient with an antenatal diagnosis that included bilateral congenital talipes equinovarus, agenesis of the left tibia, and atrioventricular communication with normal karyotype. The facies were normal at birth. Radiographs confirmed the absence of the third ray of the left hand and the absence of the left tibia, with widening of the fibula, type 5C in Paley classification, and bilateral congenital talipes equinovarus. Evidence Level: IV

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Introducción: Las Mucopolisacaridosis (MPS) son enfermedades de depósito lisosomal que se caracterizan por la acumulación excesiva de sulfato de Glucosaminoglicanos (GAGs) en órganos y tejidos, debido a la alteración en los genes que codifican para enzimas involucradas en la degradación lisosomal de glucosaminoglicanos. Se reconocen siete tipos distintos de trastornos de MPS (I, II, III, IV, VI, VII y IX) con 11 deficiencias específicas de enzimas lisosomales. El país no tiene datos exactos sobre la carga de la enfermedad, ni datos de frecuencia alélica que permita conocer la presencia de variantes poblacionales y posibles individuos afectados y portadores. Objetivo: Determinar la frecuencia alélica poblacional de las variantes del complejo MPS en una población sin diagnóstico clínico y molecular de esta patología. Materiales y métodos: Estudio descriptivo observacional donde se determinó la frecuencia alélica de variantes presentes en los genes IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, GLB1, ARSB ,GUSB ,HYAL1, asociados a MPS por medio de la secuenciación de 320 exomas completos de pacientes sin diagnóstico clínico de MPS del Suroccidente Colombiano; los resultados fueron tabulados y fueron utilizadas fórmulas de frecuencia alélica para determinar los valores asociados a cada uno de los genes. Resultados: Se reportaron 509 alelos asociadas al complejo MPS, de las cuales 262 no se habían informado previamente. Los genes con presencia alélica más frecuentes fueron IDUA, GLB1 y GALNS, involucrados en MPS I y MPS IV A / B. Las frecuencias totales oscilaron entre 0,00393 (2 alelos) y 0,47937 (248 alelos). Estos estudios nos permiten conocer la frecuencia poblacional de cada una de las variantes asociadas al complejo MPS, lo que facilita la identificación oportuna de posibles pacientes, y portadores, realizar intervenciones oportunas que incluya además asesoramiento genético. Conclusiones: Con el avance en los métodos diagnósticos genómicos es posible ampliar el conocimiento sobre el impacto de presencia de variantes de los genes asociados al complejo MPS en nuestra población, identificación e instauración de programas integrales que nos acerca a la medicina de precisión.

Introduction: Mucopolysaccharidoses (MPS) are lysosomal storage diseases characterized by the excessive accumulation of glycosaminoglycan sulfate (GAGs) in organs and tissues, due to the alteration in the genes that code for enzymes involved in the lysosomal degradation of glycosaminoglycans. Seven different types of MPS disorders (I, II, III, IV, VI, VII, and IX) are recognized with 11 specific lysosomal enzyme deficiencies. Colombia does not have exact data on the burden of the disease, nor data on the allelic frequency that allows knowing the presence of population variants and possible affected individuals and carriers. Objective: To determine the population allelic frequency of the variants of the MPS complex in a population without a clinical and molecular diagnosis of this pathology. Materials and methods: An observational descriptive study was carried out where the allelic frequency of variants present in the IDUA, IDS, SGSH, NAGLU, HGSNAT, GNS, GALNS, GLB1, ARSB, GUSB, HYAL1 genes associated with MPS was determined by means of the sequencing of 320 exomes from patients without a clinical diagnosis of MPS from the Southwest of Colombia; the results were tabulated and allelic frequency formulas were used to determine the values associated with each of the genes. Results: 509 alleles associated with the MPS complex were reported, of which 262 have not been previously reported. The genes with the most frequent allelic presence were IDUA, GLB1 and GALNS, involved in MPS I and MPS IV A. These studies allow us to know the population frequency of each of the variants associated with the MPS complex, which facilitates the timely identification of possible patients and carriers, and to carry out timely interventions that also include genetic counseling. Conclusions: With the advancement in genomic diagnostic methods, it is possible to expand the knowledge about the impact of the presence of variants of the genes associated with the MPS complex in our population, identification and establishment of comprehensive programs that bring us closer to precision medicine.

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Resumen Los aneurismas pediátricos son raros y pueden se causados por infección al dañar la pared arterial formando una saculación ciega contigua a su lumen denominada pseudoaneurisma micótico. La mayoría de los casos reportados son de pacientes ancianos con comorbilidades y los agentes causantes más frecuentes son Staphylococcus spp, Salmonella spp, Streptococcus spp y raramente hongos. Se presenta el caso de un niño de 3 años con: diagnóstico reciente de leucemia linfoblástica aguda de precursores B en remisión; alto riesgo de recaída por tratamiento incompleto y antecedente de bacteremia por Staphylococcus epidermidis y fungemia por Cándida tropicalis; vegetaciones cardiacas que hacen embolismo a hígado, bazo, pulmón y cerebro, y pseudoaneurisma micótico parcialmente trombosado de la arteria ilíaca común y externa. El diagnóstico temprano de esta entidad es de vital importancia por el riesgo de ruptura y el manejo quirúrgico dependerá de la localización, el tamaño y las complicaciones asociadas.

Abstract Pediatric aneurysms are rare and can be caused for damaging of the arterial wall secondary to an infection, forming a blind sacculation contiguous to its lumen called mycotic pseudoaneurysm. The majority of reported cases are from elderly patients with comorbidities. The most frequent involucre microorganisms are Staphylococcus spp, Salmonella spp, Streptococcus spp and rarely fungi. We present the case of a 3-year-old boy, with a recent diagnosis of acute lymphoblastic leukemia of B precursors in remission, with a high risk of relapse due to incomplete treatment and a history of bacteremia due to Staphylococcus epidermidis and fungemia due to Candida tropicalis; with cardiac vegetations that produce liver, spleen, lung and brain embolism, in whom a partially thrombosed mycotic pseudoaneurysm of the common and external iliac artery is found. The early diagnosis of this entity is of vital importance because of the risk of rupture. Surgical management will depend on the location, size and associated complications.

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A study published in 2012 estimated incidence of MPS IVA, in 0.68 cases per 100, 000 live births in Colombia, and according to the Colombian Fund for High-Cost Diseases, in 2014 there were 15 people diagnosed with MPS IV. To enhance the knowledge of the disease in the country, we aimed to characterize clinical and molecular findings in 12 MPS IVA patients. Twelve patients were included in the study, with most patients of female gender (n = 7, 58,3%), age range 2 to 28 years, average weight 26 kg (17.6-43 kg), average height 97 cm (92-104 cm), average BMI 27.6 kg/m2 (19.92-47.65 kg/m2). Clinical findings were similar to those described in the literature. GALNS gene molecular analysis showed five homozygous missense mutations in exon 11 c.1156C > T or p.R386C, a single nonsense mutation in the heterozygous state c.974G > A p.W325, and heterozygous in exon 9 mutation of exon 3 c.280C > T p.R94C, missense variant reported by Ogawa in 1995 [17]. There was only one patient that presented a homozygous missense mutation in exon 9 c.901G > T p.G301C and four patients showed the heterozygous form. A heterozygous missense mutation in exon 5 c.425A > T p.H142L, which has not been previously reported, was found in a female patient, 2 years 11 months of age. The diagnosis algorithms that include molecular analysis, bioinformatic predictive tools, pharmacogenomics, and proteomics helps to improve the diagnosis, treatment, and prognosis of patients affected by MPS IVA.

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The haloacetic acids (HAAs) are the second-most prevalent class of drinking water disinfection by-products formed by chemical disinfectants. Previous studies have determined DNA damage and repair of HAA-induced lesions in mammalian and human cell lines; however, little is known of the genomic DNA and chromosome damage induced by these compounds in primary human cells. The aim of this study was to evaluate the genotoxic and clastogenic effects of the monoHAA disinfection by-products in primary human lymphocytes. All monoHAAs were genotoxic in primary human lymphocytes, the rank order of genotoxicity and cytotoxicity was IAA > BAA >> CAA. After 6 h of repair time, only 50% of the DNA damage (maximum decrease in DNA damage) was repaired compared to the control. This demonstrates that primary human lymphocytes are less efficient in repairing the induced damage by monoHAAs than previous studies with mammalian cell lines. In addition, the monoHAAs induced an increase in the chromosome aberration frequency as a measurement of the clastogenic effect of these compounds. These results coupled with genomic technologies in primary human cells and other mammalian non-cancerous cell lines may lead to the identification of biomarkers that may be employed in feedback loops to aid water chemists and engineers in the overall goal of producing safer drinking water.

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The human population is heterogeneous in genetic susceptibility, chromosomal instability and disease risk; all factors which depend on inherited genetic constitution and acquired nongenetic environmental and occupational factors. Recently, special attention has been directed to the identification of sources of potential bias in population studies of gene-environment interactions including genetic admixture. The aim of this study was to evaluate the effect of genetic admixture in the association of genetic polymorphisms and chromosome aberrations (CA) in a population exposed to organic solvents. We assessed genetic admixture via 34 genetic ancestry informative markers (AIMs) in 398 Colombian individuals. We report a statistically significant difference of higher CA frequency in individuals' below-average European component, and in individuals' above-average Native American component after adjusting for covariates. In addition, the confounding risk ratio values are ≥10% than the adjusted risk ratio, suggesting that population stratification is a confounding factor in this gene-environment association study. Furthermore, after adjusting for individual admixture proportions and covariates, the results demonstrate that glutathione-S-transferase M1 (GSTM1)-null is associated with CA frequency increase. These results suggest that gene-environment association studies that involve recently admixed populations should take into consideration population stratification as a confounding factor and suggest GSTM1-null as a genetic marker associated with CA frequency increase.

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Organic solvents are widely used as diluents or thinners for oil-paints, gasoline and other organic mixtures. We evaluated chromosome aberrations (CAs) in lymphocytes of 200 workers exposed to organic solvents and 200 referents and the influence of polymorphisms in xenobiotic-metabolism (CYP2E1, GSTM1 and GSTT1) and in DNA repair genes (XRCC1(194) Arg/Trp, XRCC1(280) Arg/His, XRCC1(399) Arg/Gln and XRCC3(241) Thr/Met). Polymorphisms were determined by PCR-RFLP. Poisson regression analysis indicates a significant CA frequency increase in exposed workers, representing a higher risk in relation to the matched referent (RR 2.15, 95% CI 1.21-1.53, p<0.001). The CA frequency in exposed workers was influenced by the polymorphic genotypes: GSTM1 null (RR 1.33, 95% CI 1.31-1.69, p<0.001), XRCC1(194) Arg/Trp, Trp/Trp (RR 1.23, 95% CI 1.08-1.40, p<0.001) and by the wild genotypes CYP2E1 C1/C1 (RR 1.20, 95% CI 1.05-1.37, p<0.001), GSTT1 positive (RR 1.49, 95% CI 1.31-1.69, p<0.001), XRCC1(280) Arg/Arg (RR 1.44, 95% CI 1.26-1.64, p<0.001) and XRCC1(241) Thr/Thr (RR 1.54, 95% CI 1.34-1.76, p=0.001). We contribute to the follow-up predictive value of individual susceptibility biomarkers and their CA frequency influence during occupational organic solvent exposure. We provide tools for surveillance and prevention strategies to reduce potential health risks in countries with a large population of car painters not using protection devices and limited organic solvents use control.

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