Clinical-functional correlation with brain volumetry in severe perinatal asphyxia: a case report.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) appears in neurological conditions where some brain areas are likely to be injured, such as deep grey matter, basal ganglia area, and white matter subcortical periventricular áreas. Moreover, modeling these brain areas in a newborn is challenging due to significant variability in the intensities associated with HIE conditions. This paper aims to evaluate functional measurements and 3D machine learning models of a given HIE case by correlating the affected brain areas with the pathophysiology and clinical neurodevelopmental. CASE PRESENTATION: A comprehensive analysis of a term infant with perinatal asphyxia using longitudinal 3D brain information from Machine Learning Models is presented. The clinical analysis revealed the perinatal asphyxia diagnosis with APGAR <5 at 5 and 10 minutes, umbilical arterial pH of 7.0 BE of -21.2 mmol / L), neonatal seizures, and invasive ventilation mechanics. Therapeutic interventions: physical, occupational, and language neurodevelopmental therapies. Epilepsy treatment: vagus nerve stimulation, levetiracetam, and phenobarbital. Furthermore, the 3D analysis showed how the volume decreases due to age, exhibiting an increasing asymmetry between hemispheres. The results of the basal ganglia area showed that thalamus asymmetry, caudate, and putamen increase over time while globus pallidus decreases. CLINICAL OUTCOMES: spastic cerebral palsy, microcephaly, treatment-refractory epilepsy. CONCLUSIONS: Slight changes in the basal ganglia and cerebellum require 3D volumetry for detection, as standard MRI examinations cannot fully reveal their complex shape variations. Quantifying these subtle neurodevelopmental changes helps in understanding their clinical implications. Besides, neurophysiological evaluations can boost neuroplasticity in children with neurological sequelae by stimulating new neuronal connections.

Clinical Heterogeneity and Different Phenotypes in Patients with SETD2 Variants: 18 New Patients and Review of the Literature.

SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and molecular features: Luscan-Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin-Pappas syndrome (RAPAS). LLS [MIM #616831] is an overgrowth disorder with multisystem involvement including intellectual disability, speech delay, autism spectrum disorder (ASD), macrocephaly, tall stature, and motor delay. RAPAS [MIM #6201551] is a recently reported multisystemic disorder characterized by severely impaired global and intellectual development, hypotonia, feeding difficulties with failure to thrive, microcephaly, and dysmorphic facial features. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and potentially endocrine. Three patients who carried the missense variant p.Arg1740Gln in SETD2 were reported with a moderately impaired intellectual disability, speech difficulties, and behavioral abnormalities. More variable findings included hypotonia and dysmorphic features. Due to the differences with the two previous phenotypes, this association was then named intellectual developmental disorder, autosomal dominant 70 [MIM 620157]. These three disorders seem to be allelic and are caused either by loss-of-function, gain-of-function, or missense variants in the SETD2 gene. Here we describe 18 new patients with variants in SETD2, most of them with the LLS phenotype, and reviewed 33 additional patients with variants in SETD2 that have been previously reported in the scientific literature. This article offers an expansion of the number of reported individuals with LLS and highlights the clinical features and the similarities and differences among the three phenotypes associated with SETD2.

Analyses of familial chylomicronemia syndrome in Pereira, Colombia 2010-2020: a cross-sectional study.

BACKGROUND AND AIM: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive metabolic disorder caused by mutations in genes involved in chylomicron metabolism. On the other hand, multifactorial chylomicronemia syndrome (MCS) is a polygenic disorder and the most frequent cause of chylomicronemia, which results from the presence of multiple genetic variants related to chylomicron metabolism, in addition to secondary factors. Indeed, the genetic determinants that predispose to MCS are the presence of a heterozygous rare variant or an accumulation of several SNPs (oligo/polygenic). However, their clinical, paraclinical, and molecular features are not well established in our country. The objective of this study was to describe the development and results of a screening program for severe hypertriglyceridemia in Colombia. METHODS: A cross-sectional study was performed. All patients aged >18 years with triglyceride levels ≥500 mg/dL from 2010 to 2020 were included. The program was developed in three stages: 1. Review of electronic records and identification of suspected cases based on laboratory findings (triglyceride levels ≥500 mg/dL); 2. Identification of suspected cases based on laboratory findings that also allowed us to exclude secondary factors; 3. Patients with FCS scores <8 were excluded. The remaining patients underwent molecular analysis. RESULTS: In total, we categorized 2415 patients as suspected clinical cases with a mean age of 53 years, of which 68% corresponded to male patients. The mean triglyceride levels were 705.37 mg/dL (standard deviation [SD] 335.9 mg/dL). After applying the FCS score, 2.4% (n = 18) of patients met the probable case definition and underwent a molecular test. Additionally, 7 patients had unique variants in the APOA5 gene (c.694 T > C; p. Ser232Pro) or in the GPIHBP1 gene (c.523G > C; p. Gly175Arg), for an apparent prevalence of familial chylomicronemia in the consulting population of 0.41 per 1.000 patients with severe HTG measurement. No previously reported pathogenic variants were detected. CONCLUSION: This study describes a screening program for the detection of severe hypertriglyceridemia. Although we identified seven patients as carriers of a variant in the APOA5 gene, we diagnosed only one patient with FCS. We believe that more programs of these characteristics should be developed in our region, given the importance of early detection of this metabolic disorder.

Hallazgos ecocardiográficos de pacientes pediátricos con mucopolisacaridosis tipo IV-A con mutación c.901G>T en el gen GALNS en un centro de salud de cuarto nivel de Colombia en el periodo de 2012-2019

La mucopolisacaridosis tipo IV-A es un trastorno de almacenamiento lisosómico poco frecuente, cuya manifestación clínica más evidente es la disostosis múltiple. Alteraciones multiorgánicas se han descrito en este tipo de pacientes, sin embargo, las manifestaciones cardiovasculares no han sido descritas con gran énfasis. Esta investigación tuvo como objetivo principal describir los hallazgos ecocardiográficos en pacientes pediátricos con mucopolisacaridosis tipo IV-A con mutación c.90iG>T en el gen GALNS. Se realizó un estudio descriptivo de serie de casos que incluyó pacientes con diagnóstico confirmado (clínico, bioquímico y molecular) de mucopolisacaridosis tipo IV-A; los pacientes asistieron a una institución hospitalaria en Pereira, Colombia, entre 2012 y 2019, donde se valoraron parámetros ecocardiográficos. Se incluyeron diez pacientes con edades comprendidas entre 3 y 18 años, media de 10. Las anomalías cardiacas identificadas fueron regurgitación mitral trivial RM en 4 de 10 pacientes, dilatación del anillo aórtico en 9 de 10, dilatación de la aorta ascendente, dilatación del arco transverso y del istmo aórtico en 1 de 10, área subaórtica levemente engrosada sin estenosis e hipertrofia ventricular izquierda concéntrica leve en 1 de 10 pacientes. La función ventricular fue normal en todos los pacientes. Los hallazgos ecocardiográficos más frecuentes fueron dilatación del anillo aórtico y regurgitación trivial de la válvula mitral, adicionalmente, pueden encontrarse válvulas mitral y aórtica engrosadas e hipertrofia ventricular izquierda, por lo que es importante una valoración periódica por cardiología pediátrica.

Mucopolysaccharidosis IV-A is a rare lysosomal storage disorder, whose most evident clinical manifestation is multiple dysostosis. Multiorgan disorders have been described in this type of patients, however, the Cardiovascular manifestations have not been described with greater emphasis. The main objective of this research was to describe the echocardiographic findings in pediatric patients with type IV-A mucopolysaccharidosis with c.901G>T mutation in the GALNS gene. A descriptive case series study was carried out, which included patients with a confirmed diagnosis (clinical, biochemical and molecular) of mucopolysaccharidosis type IV-A; the patients were attended a hospital institution in Pereira, Colombia, between 2012 and 2019, where echocardiography parameters were evaluated. Ten patients with ages ranging from 3 to 18 years, average 10, were included. The cardiac abnormalities identified were trivial mitral regurgitation in 4 of 10 patients, aortic annulus dilation in 9 of 10, dilatation of the ascending aorta, dilatation of the transverse arch and aortic isthmus in 1 of 10, slightly thickened subaortic area without stenosis and mild concentric left ventricular hypertrophy in 1 of 10 patients. Ventricular function was normal in all patients. The most frequent echocardiography findings were dilatation of the aortic annulus and trivial regurgitation of the mitral valve, additionally, thickened mitral and aortic valves and left ventricular hypertrophy may be found, so periodic evaluation by pediatric cardiology is important.

Influence of early identification and therapy on long-term outcomes in early-onset MTHFR deficiency.

MTHFR deficiency is a severe inborn error of metabolism leading to impairment of the remethylation of homocysteine to methionine. Neonatal and early-onset patients mostly exhibit a life-threatening acute neurologic deterioration. Furthermore, data on early-onset patients' long-term outcomes are scarce. The aims of this study were (1) to study and describe the clinical and laboratory parameters of early-onset MTHFR-deficient patients (i.e., ≤3 months of age) and (2) to identify predictive factors for severe neurodevelopmental outcomes in a cohort with early and late onset MTHFR-deficient patients. To this end, we conducted a retrospective, multicentric, international cohort study on 72 patients with MTHFR deficiency from 32 international metabolic centres. Characteristics of the 32 patients with early-onset MTHFR deficiency were described at time of diagnosis and at the last follow-up visit. Logistic regression analysis was used to identify predictive factors of severe neurodevelopmental outcome in a broader set of patients with early and non-early-onset MTHFR deficiency. The majority of early-onset MTHFR-deficient patients (n = 32) exhibited neurologic symptoms (76%) and feeding difficulties (70%) at time of diagnosis. At the last follow-up visit (median follow-up time of 8.1 years), 76% of treated early-onset patients (n = 29) exhibited a severe neurodevelopmental outcome. Among the whole study population of 64 patients, pre-symptomatic diagnosis was independently associated with a significantly better neurodevelopmental outcome (adjusted OR 0.004, [0.002-0.232]; p = 0.003). This study provides evidence for benefits of pre-symptomatic diagnosis and appropriate therapeutic management, highlighting the need for systematic newborn screening for MTHFR deficiency and pre-symptomatic treatment that may improve outcome.

Parental Reports of Intervention Services and Prevalence of Teasing in a Multinational Craniofacial Microsomia Pediatric Study.

ABSTRACT: Children with craniofacial microsomia (CFM) are at increased risk for educational and social concerns. This study describes intervention services and frequency of teasing in a multinational population of children with CFM. Caregivers of children with CFM ages 3 to 18 years in the US and South America were administered a questionnaire. Additional information was gathered from medical charts and photographs. Participants (N = 169) had an average age of 10.1 ±â€Š6.2 years, were primarily male (60%), and from the US (46%) or Colombia (32%). Most participants had microtia and mandibular hypoplasia (70%). They often had unilateral (71%) or bilateral (19%) hearing loss and 53% used a hearing aid. In the US, special education services were provided for 48% of participants enrolled in school; however, similar services were rare (4%) in South America and reflect differences in education systems. Access to any intervention service was higher in the US (80%) than in South America (48%). Caregivers reported children showed diagnosis awareness by an average age of 4.4 ±â€Š1.9 years. Current or past teasing was reported in 41% of the children, starting at a mean age of 6.0 ±â€Š2.4 years, and most often took place at school (86%). As half of the US participants received developmental and academic interventions, providers should screen for needs and facilitate access to services. Given diagnosis awareness at age 4 and teasing at age 6, providers are encouraged to assess for psychosocial concerns and link to resources early in treatment.

Alternative Foods in Cardio-Healthy Dietary Models That Improve Postprandial Lipemia and Insulinemia in Obese People.

Obesity is one of the major health problems worldwide. Following healthy dietary patterns can be difficult in some countries due to the lack of availability of certain foods; thus, alternative foods are needed. Our aim was to evaluate the effect of a dietary pattern consisting of fruit, avocado, whole grains, and trout (FAWGT) on postprandial insulinemia and lipemia in obese Colombian subjects. A randomized controlled crossover study was conducted, in which 44 subjects with BMI ≥ 30 kg/m2 followed either a FAWGT diet or a diet high in saturated fat and rich in processed carbohydrates. Levels of lipids and carbohydrates were measured during the postprandial state. The FAWGT diet reduced fasting insulin, VLDL, and HOMA-IR after 8 weeks (p < 0.05), while there was a lower postprandial increase in TG, VLDL, and insulin levels after both acute and chronic intake of FAWGT diet (p < 0.05). The intake of FAWGT-diet was characterized by high consumption of foods rich in fiber, MUFAs, and vitamins C and E (p < 0.05). The consumption of a diet composed of fruit, avocado, whole grains, and trout has emerged as a valid alternative to the foods included in other heart-healthy diets since it improves postprandial lipemia and insulinemia in obese people and has similar beneficial effects to these healthy models.

Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features.

The PIDDosome is a multiprotein complex, composed by the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 that induces apoptosis in response to DNA damage. In the recent years, biallelic pathogenic variants in CRADD have been associated with a neurodevelopmental disorder (MRT34; MIM 614499) characterized by pachygyria with a predominant anterior gradient, megalencephaly, epilepsy and intellectual disability. More recently, biallelic pathogenic variants in PIDD1 have been described in a few families with apparently nonsydnromic intellectual disability. Here, we aim to delineate the genetic and radio-clinical features of PIDD1-related disorder. Exome sequencing was carried out in six consanguineous families. Thorough clinical and neuroradiological evaluation was performed for all the affected individuals as well as reviewing all the data from previously reported cases. We identified five distinct novel homozygous variants (c.2584C>T p.(Arg862Trp), c.1340G>A p.(Trp447*), c.2116_2120del p.(Val706Hisfs*30), c.1564_1565delCA p.(Gln522fs*44), and c.1804_1805del p.(Gly602fs*26) in eleven subjects displaying intellectual disability, behaviorial and psychiatric features, and a typical anterior-predominant pachygyria, remarkably resembling the CRADD-related neuroimaging pattern. In summary, we outlin`e the phenotypic and molecular spectrum of PIDD1 biallelic variants supporting the evidence that the PIDD1/CRADD/caspase-2 signaling is crucial for normal gyration of the developing human neocortex as well as cognition and behavior.

Enzyme replacement therapy interruption in mucopolysaccharidosis type IVA patients and its impact in different clinical outcomes.

Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by mutations in the GALNS gene, which leads to deficient activity of N-acetylglucosamine-6-sulfate sulfatase. MPS IVA patients usually present skeletal dysplasia, coarse features, short stature, airway obstruction, cervical spinal cord compression, dental abnormalities, and cardiac valvular alterations. Enzyme replacement therapy (ERT) with elosulfase alfa is the only disease-specific treatment available for MPS IVA patients and has been shown to improve important clinical and biochemical parameters; however, little is known about the effects of ERT interruption on these patients. In this article, we report the impact of different periods of treatment interruption on clinical outcomes of 18 MPS IVA patients. All MPS IVA patients included in this case series were treated and followed up in Latin American centers and had been receiving elosulfase alfa intravenously for at least 8 months before ERT was interrupted. Different clinical parameters and assessments were evaluated at variable timepoints following therapy interruption. Altogether, our report indicates that some beneficial ERT effects in MPS IVA patients may last after different periods of treatment interruption, as cardiac and respiratory function improvements. However, worsening of important disease parameters after ERT interruption, such as the increase in uGAGs, pain, joint and skeletal aspects, and surgery indications suggests that treatment discontinuation should be avoided in order to maintain the disease as stable as possible, aiming to optimize these patients' life expectancy and quality of life.

SARS-CoV-2 and rhinovirus/enterovirus co-infection in a critically ill young adult patient in Colombia / [Coinfección por SARS-CoV-2 y rinovirus-enterovirus en una paciente adulta joven críticamente enferma en Colombia].

The current SARS-CoV-2 pandemic has caused a huge global public health problem. We report the case of a young adult patient with laboratory-confirmed SARS-CoV-2. We describe the identification of the virus and the clinical course, diagnosis, and treatment of the infection including her rapid clinical deterioration from the mild initial symptoms, which progressed to multilobar pneumonia requiring admission to the intensive care unit. This case highlights the importance of establishing a diagnosis based on the clinical findings and the patient's history bearing in mind the possibility of gastrointestinal symptoms in addition to respiratory ones. Besides, the presence of risk factors should be investigated; in this case, we proposed obesity as a possible risk factor. Furthermore, limitations in diagnostic tests and the possibility of co-infection with other respiratory pathogens are highlighted. We describe the imaging, laboratory findings, and treatment taking into account the limited current evidence.

La actual pandemia por SARS-CoV-2 ha ocasionado un enorme problema de salud pública mundial. Se reporta el caso de una paciente adulta joven con SARS-CoV-2 confirmado por laboratorio. Se describe la identificación del virus y el curso clínico, el diagnóstico y el tratamiento de la infección. La paciente tuvo un rápido deterioro clínico a partir de síntomas iniciales leves que progresaron a una neumonía multilobar que requirió su hospitalización en la unidad de cuidados intensivos. Se destaca la importancia de establecer un diagnóstico basado en la clínica y los antecedentes del paciente, y considerando los posibles síntomas gastrointestinales además de los respiratorios. Asimismo, debe indagarse sobre la presencia de factores de riesgo, en este caso, la obesidad. También se señalan las limitaciones en las pruebas diagnósticas y la posibilidad de infección concomitante con otros agentes patógenos respiratorios, así como los hallazgos en las imágenes diagnósticas, los exámenes de laboratorio y el tratamiento en el marco de la limitada información con que se cuenta actualmente.

Coinfección por SARS-CoV-2 y rinovirus-enterovirus en una paciente adulta joven críticamente enferma en Colombia / SARS-CoV-2 and rhinovirus/enterovirus co-infection in a critically ill young adult patient in Colombia

La actual pandemia por SARS-CoV-2 ha ocasionado un enorme problema de salud pública mundial. Se reporta el caso de una paciente adulta joven con SARS-CoV-2 confirmado por laboratorio. Se describe la identificación del virus y el curso clínico, el diagnóstico y el tratamiento de la infección. La paciente tuvo un rápido deterioro clínico a partir de síntomas iniciales leves que progresaron a una neumonía multilobar que requirió su hospitalización en la unidad de cuidados intensivos. Se destaca la importancia de establecer un diagnóstico basado en la clínica y los antecedentes del paciente, y considerando los posibles síntomas gastrointestinales además de los respiratorios. Asimismo, debe indagarse sobre la presencia de factores de riesgo, en este caso, la obesidad. También se señalan las limitaciones en las pruebas diagnósticas y la posibilidad de infección concomitante con otros agentes patógenos respiratorios, así como los hallazgos en las imágenes diagnósticas, los exámenes de laboratorio y el tratamiento en el marco de la limitada información con que se cuenta actualmente.

The current SARS-CoV-2 pandemic has caused a huge global public health problem. We report the case of a young adult patient with laboratory-confirmed SARS-CoV-2. We describe the identification of the virus and the clinical course, diagnosis, and treatment of the infection including her rapid clinical deterioration from the mild initial symptoms, which progressed to multilobar pneumonia requiring admission to the intensive care unit. This case highlights the importance of establishing a diagnosis based on the clinical findings and the patient's history bearing in mind the possibility of gastrointestinal symptoms in addition to respiratory ones. Besides, the presence of risk factors should be investigated; in this case, we proposed obesity as a possible risk factor. Furthermore, limitations in diagnostic tests and the possibility of co-infection with other respiratory pathogens are highlighted. We describe the imaging, laboratory findings, and treatment taking into account the limited current evidence.

22q11.2 Deletion Syndrome in Colombian Patients With Syndromic Cleft Lip and/or Palate.

The objective of this work was to identify 22q11.2 chromosomal deletion in patients with cleft lip and/or cleft palate and suggestive syndromic phenotype in Colombian patients. We studied 49 patients with cleft lip and/or cleft palate, exhibiting additional clinical findings linked to 22q11.2 deletion syndrome. All patients underwent high-resolution G-banded karyotyping, multiplex ligation-dependent probe amplification, and clinical evaluation by a geneticist. Seven patients presented 22q11.2 deletion and 2 patients had other chromosomal abnormalities. In conclusion, this study contributes with new data for genetic etiology in syndromic conditions of oral fissures.

OPCML is hypermethylated in a subset of patients with metaplastic changes in their esophagus.

OPCML hypermethylation is considered a promising cancer biomarker. We examined methylation levels in the first exon of OPCML in two patient cohorts within the esophageal adenocarcinoma and gastric adenocarcinoma cascades and in a range of cell-lines using a custom PyroMark CpG assay. Methylation levels were significantly higher in esophageal tissue with histologically confirmed glandular mucosa as compared to tissue from normal esophagi or gastro-esophageal reflux disease. Higher levels of OPCML methylation were absent in the adjacent normal esophageal tissue of patients with glandular mucosa. Higher levels of methylation were confirmed in cell-lines derived from patients with adenocarcinoma, but also detected in two cell-lines with signs of dysplasia. We validated our assay by showing no differences in methylation levels in DNA extracted from blood of patients within the gastric adenocarcinoma cascade. OPCML hypermethylation is present in a subset of patients with metaplastic changes in their esophagus.

Characterization of congenital craniofacial anomalies in a specialized hospital of Risaralda, Colombia. 2010-2014 / Caracterización de anomalías craneofaciales congénitas en hospital de cuarto nivel en Risaralda, Colombia, 2010-2014

Abstract Introduction: Congenital craniofacial malformations have a major impact on the lives of children and their relatives when the face is compromised since they may present along with cognitive deficits or altered facial appearance. There are no conclusive data on the presence of these malformations in the Coffee Region. Objective: To identify the frequency of congenital craniofacial malformations during a 4-year period in a private institution of the city of Pereira, Risaralda, Colombia. Materials and methods: Retrospective cross-sectional study. Data were collected from the medical records of243 883 patients who were attended for the first time at a private health institution of the central-western region of Colombia. Statistical analysis was performed using the R software and Excel version 2007. Results: Between January 2010 and December 2014, 1 807 patients with congenital craniofacial malformation were treated, which corresponds to 19.5% of the total of congenital anomalies, being cleft lip and palate the most frequent. Conclusion: Although congenital cranial malformations occur frequently, there is little information about its etiology. Early diagnosis can prevent future complications that lead to deterioration of health or to an additional cost to the health system.

Resumen Introducción. Los defectos craneofaciales congénitos pueden causar un impacto en la vida de los niños y de sus familias cuando comprometen el rostro. Además, pueden estar acompañados de alteración de las funciones cerebrales o de la apariencia facial. No se tienen datos concluyentes sobre la presencia de estos defectos en el Eje Cafetero. Objetivo. Identificar la frecuencia de las malformaciones craneofaciales congénitas en un periodo de cuatro años en una institución privada de la ciudad de Pereira, en Risaralda, Colombia. Materiales y métodos. Estudio trasversal retrospectivo. La información fue recolectada a través del sistema de información de historias clínicas de pacientes que consultaron por primera vez en una institución privada de salud. El análisis estadístico fue realizado mediante el software R y Microsoft Excel versión 2007. Resultados. Entre enero del 2010 y diciembre del 2014 se atendieron 1 807 pacientes con malformaciones craneofaciales congénitas, lo que corresponde al 19.5% del total de las anomalías congénitas. La hendidura labio-palatina fue la más frecuente. Conclusiones. Aunque las malformaciones craneofaciales congénitas se presentan con frecuencia, se sabe muy poco de su etiología. El diagnóstico temprano puede prevenir futuras complicaciones que deterioren la salud o que generen un sobrecosto para el sistema de salud.

Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA.

BACKGROUND: As mucopolysaccharidosis IVA (MPS IVA) is the most frequent MPS in Colombia, this paper aims to describe its clinical and mutational characteristics in 32 diagnosed patients included in this study. METHODS: Genotyping was completed by amplification and Sanger sequencing of the GALNS gene. The SWISS-model platform was used for bioinformatic analysis, and mutant proteins were generated by homology from the wild-type GALNS code 4FDI template from the Protein Data Bank (PDB) database. Docking was performed using the GalNAc6S ligand (PubChem CID: 193456) by AutoDock Vina 1.0 and visualized in PyMOL and LigPlot+. RESULTS: Eleven variants were identified, and one new pathogenic variant was described in the heterozygous state, which is consistent with genotype c. 319 G> T or p.Ala107Ser. The pathogenic variant c.901G>T or p.Gly301Cys was the most frequent mutation with 51.6% of alleles. Docking revealed affinity energy of -5.9 Kcal/mol between wild-type GALNS and the G6S ligand. Some changes were evidenced at the intermolecular interaction level, and affinity energy for each mutant decreased. CONCLUSION: Clinical variables and genotypic analysis were similar to those reported for other world populations. Genotypic data showed greater allelic heterogeneity than those previously reported. Bioinformatics tools showed differences in the binding interactions of mutant proteins with the G6S ligand, in regard the wild-type GALNS.

Factores asociados a malformaciones congénitas: En un centro de tercer nivel región centro occidental - Colombia (ECLAMC) / Risk Factors associated with congenital malformations: in a center of high complexity in a coffee region area in Colombia

Resumen: determinar la asociación entre factores sociodemográficos, exposición a teratógenos y enfermedad materna, con la presencia de malformaciones congénitas en un centro de tercer nivel de la región centro occidental de Colombia durante el año 2013. Métodos: se realizó un estudio analítico tipo casos y controles. Se analizaron variables maternas y del recién nacido, las cuales se presentaron como frecuencias y proporciones y se evaluaron usando las pruebas de Chi2(x2) y exacta de Fisher. Para determinar la asociación entre cada variable se calculó el Odds Ratio (OR) crudo, y Odds Ratio (ORa) ajustado para las variables que presentaron una diferencia estadísticamente significativa, posterior a esto se encontró mediante test de razón de verosimilitud que no habían diferencias importantes entre el modelo completo y el reducido, mostrando entonces valores de un modelo más parsimonioso, con un test de bondad de ajuste Hosmer-Lemeshow 0.19. Resultados: Las variables sociodemográficas edad y ocupación materna, se hallaron como factor de riesgo para desarrollar malformaciones congénitas OR=7.7 (2.4 - 24.5) y OR=2,01 (1,1-3,7) respectivamente. Además en la historia obstétrica se encontró mayor riesgo al tener ganancia de peso mayor al ideal con OR=3.0a (1.3-6.7) y una ganancia de peso menor a lo ideal OR= 2.3a(1.1-4.5) y como factores protectores ser hijo del mismo padre y fácil concepción con OR=0,37C (0,2-0.8) P=0.007 y OR=0,20a (0,1-0,7), Conclusión: la edad mayor de 35 años, trabajar fuera y ganancias de peso mayores o inferiores a lo ideal, fueron los principales factores de riesgo para malformaciones congénitas en este estudio y la fácil concepción se encontró como factor protector para dicha condición del neonato.

Objective: to determine the association between sociodemographic factors, exposure to teratogens and maternal disease, with the presence of congenital malformations in a third-level center in the central western region of Colombia during the year 2013. Methods: An analytical case-control study was conducted And controls. We analyzed maternal and newborn variables, which were presented as frequencies and proportions and were evaluated using Chi2 (x2) and Fisher’s exact tests. To determine the association between each variable we calculated the Odds Ratio (OR) crude, and Odds Ratio (ORa) adjusted for the variables that presented a statistically significant difference, after this it was found by test of likelihood ratio that no differences were found Important between the complete and the reduced model, showing values of a more parsimonious model, with a goodness-of-fit test Hosmer-Lemeshow 0.19. Results: sociodemographic variables age and maternal occupation were found to be a risk for developing congenital malformations OR= 7.7 (2.4-24.5) and OR=2.01 (1.13-3.69), respectively. In the obstetric history, greater risk was found to have greater weight gain than the ideal with OR = 3.0a (1.3-6.7) and a weight gain lower than the ideal OR = 2.3a (1.1-4.9) and as protective factors being Child of the same father and conceive easy OR = 0.37C (0.2-0.8) P = 0.007 and OR = 0.20a (0.1-0.7), Conclusion: Age over 35 years, work outside and A weight gain greater than ideal, or weight gain less than ideal, are major risk factors for congenital malformations found in this study, easy conception is found as a protective factor for congenital malformations.

Síndrome Lucey-Driscoll - Reporte de caso / Lucey-Driscoll Syndrome - Case Report

La hiperbilirrubinemia no conjugada es una condición producida por una alteración en el proceso de conjugación y excreción de la bilirrubina. La glucoronosiltransferasa uridin difosfato es la responsable en la conjugación de la bilirrubina, es codificada por el gen de UGT1A1 localizado en el brazo q del cromosoma 2 locus 37.1. La variación genética del UGT1A1 puede producir diferentes fenotipos desde el más severo llamado Sindrome Crigler-Najjar Tipo I y II, pasando por el Sindrome de Gilbert; hasta una hiperbilirrubinemia transitoria neonatal o síndrome LUCEY-DRISCOLL (HBLRTFN) fenotipo OMIM 237900 con producción de kernicterus y parálisis cerebral pero con resolución espontánea, todos ellos de herencia autosómica recesiva causada por mutación homocigota o heterocigota en el gen UGT1A1. En este reporte se presenta un caso en un recién nacido que a los 7 días presenta hiperbilirrubinemia severa con kernicterus, y la prueba genética muestra mutación heterocigota del *28 del gen UGT1A1

Unconjugated hyperbilirubinemia is produced by alteration in conjugation and excretion process of bilirubin. Glucoronosiltransferasa Uridine diphosphate enzyme is involved in bilirubin conjugation. Is encoded by the UGT1A1 gene located in chromosome 2q locus 37.1. UGT1A1 genetic variation can produce different phenotypes Crigler-Najjar Syndrome Type I and II, Gilbert Syndrome, and hyperbilirubinemia transited familial LUCEY-DRISCOLL (HBLRTFN) syndrome with kernicterus production but with spontaneous resolution, all autosomal recessive. We present here a case of newborn 7 days old with severe hyperbilirubinemia , kernicterus, and genetic testing shows heterozygous mutation of the UGT1A1 * 28 gene

[Prevalence of birth defects in Risaralda, 2010-2013].

INTRODUCTION: The data regarding birth defects at local levels in developing countries like Colombia are scarce. OBJECTIVE: To describe the profile of congenital abnormalities in the province of Risaralda, Colombia. MATERIALS AND METHODS: We included the information on infants with structural and functional abnormalities at birth between June, 2010, and December, 2013, from records of the Instituto Nacional de Salud, and compared it with those of children born in the same period in a local clinic participating in the Collaborative Study of Congenital Malformations. We analyzed the data using Stata 10®. RESULTS: We found a prevalence of nine defects per 1,000 newborns from the total live births in Risaralda. The local clinic registered in the Collaborative Study of Congenital Malformations registered a prevalence of 34 defects per 1,000 births. Most frequent defects were heart defects, followed by cleft lip and palate, abdominal wall defects, skeletal dysplasia, hydrocephalus, polydactyly and Down syndrome. CONCLUSIONS: Having a baseline on the prevalence of congenital defects in Risaralda is very useful in the design of prevention policies oriented to decrease congenital defects incidence and severity. Inclusion of maternity hospitals in the Collaborative Study of Congenital Malformations strengthens national recording and reporting of birth defects.

Prevalencia de defectos congénitos en Risaralda, 2010-2013 / Prevalence of birth defects in Risaralda, 2010-2013

Resumen Introducción. Los datos sobre defectos congénitos en el ámbito regional de los países en desarrollo como Colombia son escasos. Objetivo. Describir la prevalencia de anomalías congénitas en el departamento de Risaralda, Colombia. Materiales y métodos. Se incluyeron los neonatos con defectos estructurales y funcionales entre junio de 2010 y diciembre de 2013, cuyos casos fueron notificados al Instituto Nacional de Salud por ser de interés en salud pública. Se compararon con los nacidos en el mismo periodo en una clínica de la región inscrita en el Estudio Colaborativo de Malformaciones Congénitas. Los datos se analizaron con el programa Stata 10(r). Resultados. La prevalencia entre los nacidos vivos en el periodo de estudio fue de nueve casos por cada 1.000 recién nacidos en el departamento. En la clínica inscrita en el Estudio Colaborativo de Malformaciones Congénitas, se encontró una prevalencia de 34 casos por cada 1.000 nacimientos; el primer lugar lo ocuparon las cardiopatías, seguidas por el labio y paladar hendido, los defectos de la pared abdominal (no especificados), la displasia esquelética, la hidrocefalia, la polidactilia y el síndrome de Down. Conclusión. El establecimiento de una línea de base sobre la prevalencia de los defectos congénitos en Risaralda es de gran utilidad para la adopción de políticas preventivas que lleven a la disminución de la incidencia y de la gravedad de las discapacidades; la inclusión de los hospitales materno-infantiles en la red del Estudio Colaborativo de Malformaciones Congénitas mejora el registro nacional y la notificación de los defectos congénitos.

Abstract Introduction: The data regarding birth defects at local levels in developing countries like Colombia are scarce. Objective: To describe the profile of congenital abnormalities in the province of Risaralda, Colombia. Materials and methods: We included the information on infants with structural and functional abnormalities at birth between June, 2010, and December, 2013, from records of the Instituto Nacional de Salud, and compared it with those of children born in the same period in a local clinic participating in the Collaborative Study of Congenital Malformations. We analyzed the data using Stata 10(r). Results: We found a prevalence of nine defects per 1,000 newborns from the total live births in Risaralda. The local clinic registered in the Collaborative Study of Congenital Malformations registered a prevalence of 34 defects per 1,000 births. Most frequent defects were heart defects, followed by cleft lip and palate, abdominal wall defects, skeletal dysplasia, hydrocephalus, polydactyly and Down syndrome. Conclusions: Having a baseline on the prevalence of congenital defects in Risaralda is very useful in the design of prevention policies oriented to decrease congenital defects incidence and severity. Inclusion of maternity hospitals in the Collaborative Study of Congenital Malformations strengthens national recording and reporting of birth defects.