Daniela Arturo-Terranova

Introduction: Alzheimer's Disease (AD) is the most common cause of dementia worldwide and a chronic neurodegenerative disorder with well-established pathophysiological mechanisms. In Colombia, its prevalence is increasing, but in the southwestern region, information on its clinical course is scarce, limiting adequate care and public health strategies. This study aimed to describe the frequency and characteristics of genetic variants in AD candidate genes in a population in southwestern Colombia without a clinical diagnosis of the disease. Methods: A descriptive observational analysis was conducted on 320 whole exomes from patients without a clinical diagnosis of AD. Reported genomic variants in the APOE, ABCA7, APP, PSEN1, PSEN2, and CLU genes were examined for allele frequency, clinical significance, and interaction network predictions to assess their genetic impact on the population. Results: We identified 294 genetic variants, including 267 previously unreported. Among the 27 variants reported in ClinVar, most lacked a definitive clinical interpretation and were classified as Variants of Uncertain Significance (VUS) or as variants without a defined clinical significance in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG). ABCA7 gene had the highest frequency of variants (n=164), and the PSEN1 gene had the lowest (n=14). While most variants lacked clinical significance, the APOE c.487C>T (p.Arg163Cys) variant was identified as likely pathogenic. Discussion: The genetics of AD are complex and contribute to a predisposition to developing the disease; hence, the importance of conducting studies in our Colombian population, which is characterized by great genetic variability. In our study, we identified 267 unreported variants associated with the genes APOE, ABCA7, APP, PSEN1, PSEN2, and CLU. The lack of updated data in our population underscores the need for further research to determine their clinical impact. conclusion: The present study identified germline variants associated with AD in a population from southwestern Colombia, many of which have not been previously studied. It suggests a unique genetic profile is circulating in this region. It highlights a likely pathogenic variant in the APOE gene (c.487C>T, p.Arg163Cys) linked to familial hyperlipoproteinemia type 3. These findings may facilitate early genetic diagnosis, risk prediction, more rigorous clinical monitoring, and advances in personalized medicine, biomarkers, and targeted therapies. It is important to conduct periodic reviews to reevaluate variants of uncertain significance as scientific knowledge advances. Conclusion: This research contributes to characterizing AD genetic variability in the Colombian population and identifies several previously unreported variants. According to our results, we recommend studying their potential functional and clinical impact to improve early diagnosis and support the development of targeted therapies, thereby contributing to a better understanding of the disease in southwestern Colombia.

El síndrome de Poretti-Boltshauser (PTBHS), es un trastorno autosómico recesivo, cuyas manifestaciones incluyen hipoplasia del vermis cerebeloso, discapacidad intelectual con apraxia oculomotora, displasia y quistes cerebelosos. El fenotipo se origina a partir de variantes patogénicas en el gen LAMA1, responsable de codificar la proteína Laminina alfa-1. Objetivo: describir y reportar a la literatura mundial el caso clínico de un lactante menor con PTBHS. Caso clínico: se reporta caso de lactante menor, quien presentó apneas, síntomas de respiratorios y características físicas distintivas. Los estudios de imagen revelaron anomalías cerebrales, como agenesia del cuerpo calloso y ventriculomegalia. Se realizó una secuenciación genómica completa, identificando dos mutaciones en el gen LAMA1 (p.Arg2128Trp y p.Pro839Ser), las cuales no han sido descritas en la literatura, ni reportadas en bases de datos poblacionales como Clinvar o gnomAD. El análisis bioinformático sugirió que estas variantes eran patogénicas y estaban asociadas con los síntomas clínicos observados, como la hipoplasia del vermis cerebeloso, la discapacidad intelectual y las anomalías cerebelosas. Conclusión: se representa la primera correlación fenotipo/genotipo documentada en un lactante con PTBHS. Se resalta la importancia de estudios genómicos que incluya la bioinformática y la reclasificación de significancia de las variantes genéticas encontradas en estudios moleculares teniendo en cuenta la clínica y demás ayudas diagnósticas paraclínicas que permita instaurar un diagnóstico oportuno y un tratamiento adecuado basado en la medicina 4P (personalizada, predictiva, preventiva y participativa).

Gaucher disease is a rare lysosomal storage disorder whose implications for the stomatognathic system remain poorly explored. This study presents a bibliometric analysis aimed at characterizing the scientific production related to GD, bone involvement, and diagnosis, with particular emphasis on the representation of oral and maxillofacial manifestations. A systematic search was conducted in the Scopus database, retrieving peer-reviewed publications on Gaucher disease and oral/maxillofacial health published between 1970 and 2026. Bibliometric analysis and knowledge mapping were performed using VOSviewer. Keyword co-occurrence networks and temporal visualizations were generated using full counting and association strength normalization to identify thematic clusters, main collaboration structures, and research gaps in the literature. Publications showed a centralized geographic distribution led by the US, alongside the UK, Israel, and European nations. Bibliometric mapping of 42 high-frequency keywords revealed three main thematic axes: therapeutic/molecular foundations (dominated by enzyme replacement therapy), systemic skeletal manifestations (focused on MRI, osteoporosis, and bone marrow infiltration), and demographic population traits. Temporal overlay analysis indicated a shift from early prenatal diagnosis to skeletal complications, yet oral, dental, and craniofacial manifestations remained virtually absent. This persistent thematic gap highlights a disconnect between clinical literature-which documents jaw involvement, bone resorption, and surgical risks-and mainstream research prioritization. The lack of interdisciplinary integration excludes dental professionals from early screening and comprehensive management. Future studies must incorporate multi-database searches and advanced 3D morphometrics to optimize multidisciplinary patient care.

Central nervous system (CNS) cryptococcosis caused by Cryptococcus neoformans is a severe opportunistic infection that primarily affects individuals with impaired cellular immunity. Although the classic presentation includes headache, fever, and meningeal signs, chronically immunosuppressed patients may develop atypical neuropsychiatric manifestations, leading to diagnostic delays. We report the case of a 53-year-old man with rheumatoid arthritis (RA) receiving long-term prednisolone and etanercept therapy, who presented with a 7-day history of depressive mood, anhedonia, social withdrawal, irritability, and progressive confusion. Neurological examination revealed disorientation without focal deficits. Brain imaging showed only mild cortical atrophy, and cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis, low glucose, and elevated protein levels. Multiplex PCR (FilmArray^®) of CSF identified Cryptococcus neoformans, CSF positive to C. neoformans. The patient was treated with liposomal amphotericin B followed by fluconazole, resulting in gradual improvement of both neurological and psychiatric symptoms. This case highlights an unusual presentation of CNS cryptococcosis in a non-HIV immunosuppressed patient with RA, emphasizing that acute psychiatric or cognitive changes can be the predominant manifestation. Clinicians should consider fungal infections in the differential diagnosis of acute neuropsychiatric symptoms in patients receiving chronic corticosteroid and biologic therapy. Early recognition and molecular diagnosis can facilitate timely antifungal treatment, potentially improving prognosis and reducing morbidity associated with delayed therapy. This report underscores the importance of awareness of atypical presentations of opportunistic infections in immunosuppressed populations.

Introducción: El síndrome de Schinzel-Giedion (SGS) es un trastorno autosómico dominante ultrarraro que se caracteriza por un fenotipo con compromiso cognitivo severo, rasgos faciales distintivos y múltiples anomalías congénitas que involucra los sistemas cardiaco, esquelético, genitourinario y renal, además de asociarse a convulsiones y mortalidad prematura. Es causado por variantes en el gen SETBP1 que codifica para la proteína de unión a SET. Se han encontrado aproximadamente 88 casos a escala mundial, 33 de estos pacientes con diagnóstico molecular. El objetivo es describir a un paciente pediátrico colombiano con SGS en sus dimensiones clínica, imagenológica y molecular. Caso clínico: Se reporta el caso de un paciente masculino de 3 años y 6 meses, producto de primer embarazo de padres no consanguíneos sin antecedentes perinatales ni familiares, que presentó cuadro de convulsiones refractarias al manejo con inicio en el periodo neonatal, con facies dismórfica, retraso del neurodesarrollo, hipotonía, microcefalia y malformaciones genitales. Se le realizó estudio molecular mediante secuenciación del exoma completo y estudio genómico- bioinformático utilizando tecnología in-silico, encontrando una variante missense (c.2612T > C; p.Ile871Thr) en el gen SETBP1; por bioinformática se determinó que esta variante tenía un significado clínico patogénico. Conclusión: Este caso corresponde al primer reporte colombiano del SGS que logra proporcionar datos actualizados de la enfermedad, incluyendo presentación clínica, técnicas de neuroimagen y confirmación por estudios moleculares, bioinformáticos, que aportan al avance en el diagnóstico temprano.

Mucopolysaccharidosis IV-A (MPS IV-A) is an autosomal recessive genetic disorder caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase, leading to the accumulation of chondroitin-6-sulfate (C6S) and keratan sulfate (KS). This is a rare disease, and, in Colombia, it is classified as an orphan disease under Resolution 023 of 2023. Notably, its incidence in Colombia is higher than that reported in other countries worldwide. Genomic analysis of the GALNS gene has identified more than 400 variants in affected individuals, enabling genotype-phenotype correlations. We report the case of a patient who was initially presented at the age of 5 with short stature, lower limb dysmetria, and genu valgum. Physical examination revealed coarse facial features, a short neck, pectus carinatum, multiple joint deformities, and ligamentous hyperlaxity. Enzymatic activity of GALNS was reported at 0.06 mmol/mL/hour, and complete sequencing of the GALNS gene was performed using next-generation sequencing (NGS) technology, identifying the homozygous variant c.239C>T (p.Ser80Leu), which is associated with MPS IV-A. A bioinformatic analysis classified this variant as pathogenic. This case underscores the importance of clinical presentation, the use of diagnostic methodologies, and confirmation through molecular and bioinformatic studies for an accurate and timely diagnosis, as well as the critical value of appropriate clinical follow-up.

Gaucher disease type 1 (GD1) is the most common lysosomal storage disorder, characterized by hepatomegaly, splenomegaly, anemia, thrombocytopenia, and skeletal manifestations, which significantly affect quality of life. This systematic review aimed to assess the current state of the disease, focusing on skeletal manifestations. A systematic search was conducted between 2000 and February 2024 in multiple languages using PRISMA-ScR and JBI methods. A total of 96 studies were identified: 23 systematic reviews, 23 descriptive studies, 17 case reports, 13 experimental studies, 10 retrospective studies, 4 observational studies, 4 prospective studies, and 2 cross-sectional studies. The highest number of articles on the topic was published in 2015, and the countries with the most publications were the USA, Italy, Brazil, and Argentina over the 23 years covered in the search. These studies cover various aspects of GD1, including skeletal features, patient phenotypes, clinical annotations, diagnostics, therapies, and patient perspectives. Despite advances, challenges such as disease heterogeneity and inconsistent results persist. This review underscores the importance of further research to improve understanding and management of GD1, with an emphasis on skeletal manifestations.

Introducción: La deficiencia del complejo I es el defecto bioquímico más común del sistema de fosforilación oxidativa, se ha asociado con variantes patogénicas en el gen TMEM126B que codifica para el factor de ensamblaje TMEM126B a nivel mitocondrial y que da lugar a una presentación fenotípica diversa como intolerancia al ejercicio, debilidad muscular, acidemia hiperláctica, miocardiopatía hipertrófica y acidosis tubular renal. Objetivo: Reportar nuevas variantes en el gen TMEM126B identificadas en un paciente pediátrico masculino con deficiencia del complejo I. Materiales y Métodos: Paciente masculino de 11 meses con antecedente de hipotonía congénita. Se le realizó la secuenciación del exoma completo + CNV por NGS; las variantes reportadas fueron analizadas por softwares bioinformáticos como Mutation Taster, UMD-Predictor, POLYPHEN, SIFT, DANN, Human Splicing Finder y Varsome. Finalmente, se construyó una red de interacción génica por el programa GeneMania para identificar asociaciones génicas cercanas. Resultados: Se identificaron las variantes c.222_223del (p.Gln74HisfsTer26) y c.509+61del (p?) en el gen TMEM126B. Estas variantes no están reportadas en bases de datos poblaciones y tampoco descritas en la literatura mundial. A partir del análisis en softwares bioinformáticos se concluyó que tienen significancia probablemente patogénica e incierta, respectivamente. La red de interacción mostró que TMEM126B está directamente relacionado con la familia de genes TMEM126, DYNC12 y NDUFAF1. Conclusión: El reporte de nuevas variantes en el gen TMEM126B mediante el uso de técnicas genómicas-bioinformáticas permiten ampliar el espectro de variantes genéticas, especialmente las intrónicas, contribuir al diagnóstico dirigido de pacientes con enfermedades mitocondriales y brindar una atención individualizada y hacer un acercamiento a la medicina de precisión.

Introducción: La enfermedad de Gaucher tipo 1 (EG1) es una enfermedad genética causada por la deficiencia enzimática de β-glucocerebrosidasa, lo que conduce a la acumulación de esfingolípidos en el organismo. La afectación ósea es frecuente en la EG, provocando dolor, necrosis e incluso fracturas o déficit de crecimiento, con cirugías dolorosas y disminución progresiva de la calidad de vida. Metodología: estudio observacional retrospectivo con 30 pacientes diagnosticados con EG1 del suroccidente colombiano, recopilando datos demográficos, clínicos, paraclínicos y moleculares. Resultados y discusión: La edad media de los pacientes fue de 35 años, el 23% con antecedentes familiares de EG1. El síntoma inicial en el 87% de los pacientes fue visceromegalia y citopenias. El tiempo promedio desde el inicio de los síntomas hasta el diagnóstico fue de 7 años. Los pacientes presentaron enfermedades hematológicas (37%), renales (3%), neurológicas (7%) y óseas (33%). La actividad media de β-glucosidasa fue de 2.33 μmol/hr/ml, y el tiempo promedio entre diagnóstico y tratamiento fue de 1.33 años. Todos los pacientes mostraron actividad enzimática reducida al diagnóstico. El 76.6% recibió terapia específica, incluyendo Terapia de Reemplazo Enzimático (TRE) y Terapia de Reducción de Sustrato (TRS). El análisis genético reveló homocigosis en 4%, heterocigotos compuestos en 52% y heterocigotos simples en 40%. Se identificaron 13 variantes patogénicas, siendo la más frecuente p.Asn409Ser (42%). Conclusión: Este es el primer estudio colombiano que correlaciona variables demográficas, clínicas, paraclínicas y moleculares en pacientes con EG1, proporcionando una base de datos que permite un abordaje multimodal para mejorar el diagnóstico y tratamiento de la EG1 en Colombia, acordándonos a la medicina de precisión

Introduction: Gaucher disease (GD1) is caused by the enzymatic deficiency of β-glucocerebrosidase. This leads to accumulation of sphingolipids in organs, such as the liver, spleen, and bone marrow. Bone involvement is frequent in GD1, causing pain, necrosis and even fractures or growth deficits in children, leading to painful surgeries and progressive decrease in quality of life. Methodology: A non-experimental retrospective observational study was performed using a database of 30 patients with clinical suspicion and enzymatic and/or molecular confirmation of GD1; the numbers and percentages of occurrence for each sign were determined. Results: Bone pain was the most common symptom and was reported in 23% of the sample. 13/30 (43%) patients had report of at least one radiograph requested during the study : 6 of them, with some bone alteration, being the most frequent : increases in acetabular coverage with signs of femoroacetabular impingement, decrease in height and morphology and Erlenmeyer deformity; 14/30 (48%) of the patients presented at least one result of Magnetic Resonance Imaging (MRI); in the femur MRI of 4 patients there was a decrease in the signal intensity of the bone marrow, both in T1 and T2 sequences, involving various bone areas and changes of infiltrative bone disease; finally in 7/30 (7. 5%) presented at least one bone densitometry result (DEXA): 3 presented low bone mineralization. The patients who present the p. Asn409Ser allele may present more predisposition to bone disease. Conclusion: The present study highlights the importance of early diagnosis, to access timely treatment, to prevent bone complications typical of the disease, improving prognosis, quality of life and morbi-mortality in GD1.