Introduction:Mucopolysaccharidosis type VI, also known as Maroteaux-Lamy syndrome (#OMIM 253200), is a rare autosomal recessive genetic disorder due to deficient activity of the enzyme N-acetylgalactosamine 4-sulfatase (arylsulfatase B) required for the breakdown of dermatan sulfate and chondroitin sulfate. Patient:Report of a female patient started on enzyme replacement therapy at 17 months of age. At the time of diagnosis (14 months), the patient presented mild corneal opacity and significant thoracolumbar kyphosis, but no visceral involvement or growth arrest. At 73 months of treatment, weight was normal, although the patient was in a low height percentile. The patient showed adequate neural development, with improvement in lumbar spine and joint involvement. Corneal compromise or valvular disease progression was not evident. Conclusion:Early and timely diagnosis and treatment with enzyme replacement therapy are essential, as the means to change the natural history of the disease, avoiding comorbidities and improving final prognosis.
Respiratory disease is the leading cause of death in the UK. Methods for assessing pulmonary function and chest wall movement are essential for accurate diagnosis, as well as monitoring response to treatment, operative procedures and rehabilitation. Despite this, there is a lack of low-cost devices for rapid assessment. Spirometry is used to measure air flow expired, but cannot infer or directly measure full chest wall motion. This paper presents the development of a low-cost chest wall motion assessment system. The prototype was developed using four Microsoft Kinect sensors to create a 3D time-varying representation of a patient's torso. An evaluation of the system in two phases is also presented. Initially, static volume of a resuscitation mannequin with that of a Nikon laser scanner is performed. This showed the system has slight underprediction of 0.441 %. Next, a dynamic analysis through the comparison of results from the prototype and a spirometer in nine cystic fibrosis patients and thirteen healthy subjects was performed. This showed an agreement with correlation coefficients above 0.8656 in all participants. The system shows promise as a method for assessing respiratory disease in a cost-effective and timely manner. Further work must now be performed to develop the prototype and provide further evaluations.
Abstract Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage‐sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF , including four individuals with inherited changes in BPTF . In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi‐faceted complications due to haploinsufficiency of BPTF .
Introduccion: el sindrome de Rothmund-Thomson (RT) es una rara genodermatosis con patron de herencia AR, caracterizado por Poiquiloderma (rash cutaneo, atrofia de piel, telangectasias, hipo e hiperpigmentacion) y un amplio espectro de signos clinicos como baja talla, cejas y pestanas escasas o ausentes, catarata juvenil, anormalidades esqueleticas, envejecimiento prematuro y predisposicion aumentada a tumores malignos1,2. Descripcion de caso: paciente de sexo masculino, edad 2 anos, padres no consanguineos, parto normal a termino, peso 1300 gr, talla 43 cm, baja talla de inicio prenatal, pelo, cejas y pestanas escasas desde el nacimiento, a los 3 meses presenta lesiones eritematosas lineares no pruriginosas en cara, a los 8 meses lesiones ampollosas eritematosas en torax y extremidades, desarrollo psicomotor normal. Examen fisico talla baja proporcionada, pelo y pestanas escasas, madarosis, filtrum corto, microdoncia y braquidactilia. Multiples lesiones maculopapulares violaceas hipocromicas en cara asociadas a Telan gectasias, lesiones hipercromicas planas en region perineal. Biopsia de piel reporta hiperqueratosis, hipergranulosis y queratinocitos apoptoticos, dermis superficial sin anexos. Ecografia de abdomen, Rx de torax y huesos largos normales. Estudio molecular para el gen RECQL4 reportando dos polimorfismos, sin mutaciones en el mismo. Discusion: hasta la fecha no hay datos precisos de incidencia por lo infrecuente de la enfermedad, se han reportado 300 casos en la literatura mundial1,2. Se describen 2 formas clinicas, RT tipo I caracterizado por Poiquiloderma, displasia ectodermica y cataratas juveniles; el tipo II con Poiquiloderma, defectos oseos congenitos y riesgo aumentado para cancer1. El tipo II es causado por mutaciones en el gen de la Helicasa RECQL4 y el tipo I es negativo para mutaciones en este gen y se clasifica en el grupo de las enfermedades mendelianas huerfanas. Deficiencias en las Helicasas producen altos niveles de inestabilidad genomica y pobre respuesta a estres oxidativo, llevando a envejecimiento prematuro y susceptibilidad aumentada a cancer3,4. Conclusiones: hasta la fecha es el primer caso de Sindrome RT tipo I reportado en la literatura medica indexada de Colombia, los casos de genodermatosis requieren una amplia investigacion y un acompanamiento continuo.
Maroteaux-Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is an autosomal recessive lysosomal storage disease caused by a deficient activity of the enzyme arylsulfatase B (ARSB), required to degrade dermatan sulfate. The onset and progression of the disease vary, producing a spectrum of clinical presentation. So far, 133 mutations have been reported. The aim of this study is to determine the mutations in the ARSB gene that are responsible for this disease in Colombian patients.Fourteen patients with clinical manifestations and biochemical diagnosis of MPS VI were studied, including two siblings. The 8 exons of the gene were directly sequenced from patients' DNA, and 14 mutations were found. 57% of these mutations had not been previously reported (p.H111P, p.C121R, p.G446S, p.*534W, p.S334I, p.H147P, c.900T > G, and c.1531_1553del) and 43% had been previously reported (p.G144R, p.W322*, p.G302R, p.C447F, p.L128del, and c.1143-1G > C). Of the previously reported mutations, 80% have been associated with severe phenotypes and 20% with intermediate-severe phenotypes. Bioinformatic predictions indicate that the new mutations reported in this paper are also highly deleterious.Most of the Colombian patients in this study had private mutations.
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.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+.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.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.
Xia-Gibbs syndrome is an autosomal dominant multisystem developmental disorder characterized by global developmental delay, hypotonia, obstructive sleep apnea, seizures, retrocerebellar cysts, delayed myelination, micrognathia, and mild dysmorphic features. Using whole-exome sequencing, we identified a de novo AHDC1 frameshift mutation c.2030_2030delG (p.G677Afs*52) in a Colombian patient, which was absent in both parents. Furthermore, we summarized the phenotypes of patients reported in the literature.
En la dermatologia, el cutis laxa conforma un raro y heterogeneo grupo de enfermedades cutaneas, caracterizadas por la perdida progresiva de la elasticidad en la piel, mostrando una apariencia de envejecimiento prematuro y compromiso variable de tejido conectivo elastico. Se informa el caso de un paciente de tres meses de edad de sexo masculino, sin consanguinidad en sus padres; quienes informan que el nino mostro tener desde su nacimiento: piel laxa e hipotonia generalizada, craneosinostosis, hernias inguinales bilaterales, contracturas en manos y pies, pie equino varo bilateral y agenesia del cuerpo calloso. Ante esta informacion, se considera que el caso descrito es compatible con la enfermedad cutis laxa autosomica recesiva, con fenotipo secundario a funcion anomala de la proteina mitocondrial PYCR1; tal asociacion no ha sido descrita aun en ninos colombianos
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