Search

Introduction: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children's Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings., Methods: Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the GALNS gene was sequenced for all cases., Results: 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C ( n = 10, 41.66%) and p.(Arg386Cys) ( n = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018]., Conclusion: This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Background: Rho-related BTB domain-containing protein 2 ( RHOBTB2 ) is a protein that interacts with cullin-3, a crucial E3 ubiquitin ligase for mitotic cell division. RHOBTB2 has been linked to early infantile epileptic encephalopathy, autosomal dominant type 64 (OMIM618004), in 34 reported patients., Methods: We present a case series of seven patients with RHOBTB2 -related disorders ( RHOBTB2 -RD), including a description of a novel heterozygous variant. We also reviewed previously published cases of RHOBTB2 -RD., Results: The seven patients had ages ranging from 2 years and 8 months to 26 years, and all had experienced seizures before the age of one (onset, 4-12 months, median, 4 months), including various types of seizures. All patients in this cohort also had a movement disorder (onset, 0.3-14 years, median, 1.5 years). Six of seven had a baseline movement disorder, and one of seven only had paroxysmal dystonia. Stereotypies were noted in four of six, choreodystonia in three of six, and ataxia in one case with multiple movement phenotypes at baseline. Paroxysmal movement disorders were observed in six of seven patients for whom carbamazepine or oxcarbazepine treatment was effective in controlling acute or paroxysmal movement disorders. Four patients had acute encephalopathic episodes at ages 4 (one patient) and 6 (three patients), which improved following treatment with methylprednisolone. Magnetic resonance imaging scans revealed transient fluid-attenuated inversion recovery abnormalities during these episodes, as well as myelination delay, thin corpus callosum, and brain atrophy. One patient had a novel RHOBTB2 variant (c.359G>A/p.Gly120Glu)., Conclusion: RHOBTB2 -RD is characterized by developmental delay or intellectual disability, early-onset seizures, baseline movement disorders, acute or paroxysmal motor phenomena, acquired microcephaly, and episodes of acute encephalopathy. Early onsets of focal dystonia, acute encephalopathic episodes, episodes of tongue protrusion, or peripheral vasomotor disturbances are important diagnostic clues. Treatment with carbamazepine or oxcarbazepine was found to be effective in controlling acute or paroxysmal movement disorders. Our study highlights the clinical features and treatment response of RHOBTB2 -RD., (© 2023 International Parkinson and Movement Disorder Society.)

Background: Reviews of camera surveillance systems have demonstrated ambivalent behaviors among people who die by railway suicide. Yet, only few preventive measures have been evaluated. Aims: We aimed to review incidents of suicidal behavior at a Danish railway station, install preventive measures, and monitor subsequent calls to a telephone helpline and reports of suicidal incidences. Method: Suicide incidents at Valby Station during 2012-2018 were reviewed to identify options for preventive measures. Based on these findings, signs encouraging help-seeking and other measures were implemented. Calls to the Danish helpline for suicide prevention and suicidal events at the station were subsequently monitored. Results: The review revealed locations where measures were meaningful and signs, physical barriers, and motion-sensitive lights were installed. Over the following 14 months, no suicide deaths occurred, and the signs were mentioned in 14 calls to the helpline, some of which were made by callers who were evaluated to be at high risk of suicide. Limitations: No direct link between implemented measures and observed outcomes could be established. Conclusion: Installing measures, including signs, at appropriate locations at railway platforms may encourage people in crisis to seek support.

Background: Wound healing after pectoral port implantation is a major factor determining the success or failure of the procedure. Infection and wound dehiscence can endanger the functionality of the port system and impede chemotherapy. The cosmetic result is important for patient satisfaction as well., Methods: From August 2015 to July 2017, adult patients with an indication for port implantation were entered into a prospective, randomized and controlled single-center study. The skin incision was closed either with tissue adhesive or with an intracutaneous suture. The primary endpoints were the total score of the scar evaluated by the patient and the investigator on the POSAS scale (Patient and Observer Scar Assessment Scale: 6 [normal skin] to 60 points), blinded assessment of photographic documentation by ten evaluating physicians, and the patient's reported quality of life. The calculation of case numbers was based only on the patients' overall POSAS assessment, which was tested for non-inferiority. The secondary endpoints were other complications (infection, dehiscence) and the duration of wound closure (trial registration number NCT02551510)., Results: 156 patients (60 ± 13 years, 64% women) participated in the study. The patient-assessed total POSAS score of tissue adhesive revealed non-inferiority to suturing (adhesive 11.7 ± 5.8 vs. suture 10.1 ± 4.0, p for non-inferiority <0.001). Both the investigators in their POSAS assessments and the blinded physician evaluators in their assessment of photographically documented wounds rated wound closure by suturing better than closure with tissue adhesive. No significant differences were found between groups with respect to quality of life or the frequency of wound infection or dehiscence., Conclusion: Closure of the upper cutaneous layer with tissue adhesive is a suitable and safe method of wound closure after port implantation.

It is key to expand the differential diagnosis and consider possible genetic etiologies on a patient with congenital cataracts associated with clinical features, such as leukodystrophy or polyneuropathy., Competing Interests: None of the authors declare any conflict of interest., (© 2021 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

Objectives: There is currently no established algorithm for the molecular profiling of therapy-relevant defects in salivary gland carcinomas (SGC). HER2 overexpression in a subfraction of SGC and low frequencies of EGFR mutations are known. Here, we established receptor and cell signalling profiles of 17 therapy-relevant factors and propose a molecular diagnostic algorithm for SGC., Materials and Methods: Formalin-fixed and paraffin-embedded tissue samples from SGC (n = 38) were analysed with immunohistochemistry and fluorescence in situ hybridisation (FISH)., Results: Two or more expressed receptors and/or receptor gene amplification were detectable in eight of 38 (21%) tumours: HER2 3+/AR 1+, HER3 gene amplification/AR 1+/EGFR 1+, ER 3+/AR 1+, EGFR 2+/PR 1+ and EGFR 2+/PR 1+/AR 1+. No FGFR1-3, MET, ALK1, ROS1, RET, BRAF nor VEGFA defects were detectable, and ERCC1 was not overexpressed. No PD1+ tumour-infiltrating T cells were detectable., Conclusion: Personalised therapy of patients with salivary gland carcinomas should include HER2 and EGFR signalling testing and, in negative cases, evaluation of rare potential target molecules. ERCC1 and PD1 do not appear to be reliable markers for the decision for or against chemotherapy or immunotherapy, respectively., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Children with cerebral palsy (CP) have an increased risk of vitamin D (VD) deficiency. Although there are many studies on VD and CP, there is limited information about VD supplementation in these patients., Objective: To evaluate the effect of supplementation with a single dose of VD on the plasma concentrations of 25-hydroxy-vitamin-D (25OHD) in children with CP., Patients and Method: Prospective-randomised-controlled-trial, including 30 Chilean children (19 males) with CP, median age 9.9 years (6.2-13.5). Clinical and biochemical variables including 25OHD, were recorded (time 0 and 8 weeks). Patients were allocated to the supplemented (S) group receiving 100,000 IU oral D3 at baseline, and compared with the placebo (P) group., Results: Among clinical features are highlighted: gastrostomy (60%), underweight (30%), bed-ridden (93.3%), antiepileptic drugs (70%), and 43.3% used VD metabolism inducing antiepileptics. Baseline biochemical measurements were normal. The 25OHD was insufficient in 4/30 and deficient in 6/30. 25OHD levels were not associated with the variables studied. Eight patients completed the study in the S group, and 10 in P group. The placebo and supplementation groups had no significant difference in baseline variables. Serum calcium, phosphate, and alkaline phosphatase levels at 8 weeks were normal in both groups, with no statistically significant differences. 25OHD in the P group was normal in 6/10, and insufficient+deficient in 4/10, and the S group was normal in all (8/8) (exact Fisher test P=.07)., Conclusions: A single dose of 100,000 IU VD could normalise the concentrations of 25OHD after 8 weeks of supplementation in Children with CP, but more studies are required to confirm these results., (Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)