ABSTRACT
Autosomal recessive proprotein convertase 1/3 (PC1/3) deficiency, caused by mutations in the PCSK1 gene, is characterized by severe congenital malabsorptive diarrhea, early‐onset obesity, ...and certain endocrine abnormalities. We suspected PC1/3 deficiency in a 4‐month‐old girl based on the presence of congenital diarrhea and polyuria. Sequencing the whole coding region and splice sites detected a novel homozygous PCSK1 splice‐site mutation, c.544–2A>G, in the patient. The mutation resulted in the skipping of exon 5, the generation of a premature termination codon, and nonsense‐mediated PCSK1 messenger ribonucleic acid decay, which was demonstrated in complementary DNA derived from fibroblasts.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Hyaline fibromatosis syndrome is an autosomal recessive disease caused by mutations in ANTXR2 which leads to loss of function of the transmembrane protein anthrax toxin receptor 2. It is ...distinguished by characteristic skin lesions, gingival hyperplasia, joint and bone disease, and systemic involvement.
Methods
Based on the case of an 11‐year‐old female patient with typical features of hyaline fibromatosis syndrome and the underlying pathogenic compound heterozygote variants in ANTXR2 we discuss the genetic and clinical aspects of hyaline fibromatosis syndrome.
Results
The novel mutation in ANTXR2 (c.1223T>C, p.Leu408Pro variant) seems to allow for a protracted course of the disease.
Conclusion
Our findings add to the phenotypic, genetic, and biochemical spectrum of hyaline fibromatosis syndrome.
Hyaline fibromatosis syndrome is an autosomal recessive disease caused by mutations in ANTXR2 which leads to loss of function of the transmembrane protein anthrax toxin receptor 2. It is distinguished by characteristic skin lesions, gingival hyperplasia, joint and bone disease, and systemic involvement. Based on the case of an 11‐year‐old female patient with typical features of hyaline fibromatosis syndrome and the underlying pathogenic compound heterozygote mutation (c.1223T>C, p.Leu408Pro variant) in ANTXR2 we discuss the genetic and clinical aspects of hyaline fibromatosis syndrome.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Highlights • Primary acquired gastric outlet obstruction in the paediatric age group is a rare disease. • The case of a 5-year-old boy with GOO is reported. • The patient was firstly treated with ...botulinum toxin injection then subsequently underwent Heineke-Mikulicz pyloroplasty.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with ...mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids.
We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequencing analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for the activity of caspases 3 and 7.
In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids.
We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal organoids derived from these patients had altered lipid metabolism and were susceptible to lipid-induced cell death. Expression of full-length wildtype DGAT1 or DGAT2 restored normal lipid metabolism in these cells. These findings indicate the importance of DGAT1 in fat metabolism and lipotoxicity in the intestinal epithelium. A fat-free diet might serve as the first line of therapy for patients with reduced DGAT1 expression. It is important to identify genetic variants associated with congenital diarrheal disorders for proper diagnosis and selection of treatment strategies.
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BACKGROUND:Congenital gastric antral web and congenital pyloric atresia are rare reasons of congenital gastric outlet obstruction (CGOO). Depending on the different forms, the symptoms vary from ...unspecific epigastric pain to nonbilious “projectile” vomiting, ileus and failure to thrive. Throughout the years, many different treatment options are described, like simple surgical dilatation, incision or excision of the membrane, possibly combined with a pyloroplasty.
PATIENTS AND METHODS:In this retrospective single-center observation study, we present 9 cases with different kinds of webs leading to CGOO. In a time period of 45 years (1970 to 2015) different treatment strategies and limitations of minimal invasive endoscopic treatment on the basis of complications and outcome are discussed.
RESULTS:Six patients had an incomplete antrum web. One patient suffered from a complete antrum web. In addition, in 2 patients a complete pyloric web, as well as an incomplete pyloric web was found. During the past 45 years, the treatment options for CGOO due to webs changed, and with the development of smaller and more flexible video endoscopes an endoscopic treatment has become feasible. The treatment strategy and follow-up examination was specific to every patient.
CONCLUSION:On the basis of our review, minimal endoscopic procedures in small newborns and toddlers require a high level of experience. They are technically challenging and need suitable equipment. Overall, endoscopists and pediatric surgeons should equally be prepared for all possible complications in every treatment step. The endoscopic approach to managing this unusual disease may require multiple interventions and is associated with a risk of perforation. Therefore, we are convinced that centers undertaking this treatment modality should be equipped with the proper instrumentation, prepared to perform multiple endoscopic interventions, and supported with an ability to emergently convert to surgery if required.
Elastic stable intramedullary nailing (ESIN) is the first-choice surgical technique for stabilizing various pediatric diaphyseal and selected metaphyseal fractures of the long bones. This technique ...has increasingly been applied in fractures of the small bones. Here, we report experiences with ESIN in displaced fractures of the metacarpals in children.
Retrospective data analysis of metacarpal fractures in children stabilized by ESIN in three pediatric trauma centers between 2003 and 2009. Indication for intervention was total displacement or axial deviation >10 degrees in the frontal plane and/or >30 degrees in the sagittal view.
A total of 66 cases of metacarpal fractures (51 right hand and 12 left hand) treated by ESIN were found in 63 children (mean age 13.3 years; range 4.0 to 16.1) over the study period. Of these, 55 fractures affected metacarpal 5, 6 fractures affected metacarpal 4, 3 fractures affected metacarpal 1, and 2 fractures occurred at metacarpal 2. Mean operating time was 21 minutes (range 5 to 54), titanium elastic nails were used with a diameter of 1.5 mm (n = 23), 2.0 mm (n = 42), and 2.5 mm (n = 1). Single ESIN implantation was performed in 63 cases; in 3 cases, two nails were implanted. Eleven patients received additional immobilization due to nondisplaced additional fractures of the phalanx (n = 2) or for analgetic treatment (n = 9). Five complications were registered (7.6%). In two cases recurrent fracture dislocation occurred, one of them requiring revision of the osteosynthesis. In other two cases irritation of the extensor tendons occurred, one of them requiring secondary tendon plasty. One persisting cutaneous hyposensibility after ESIN of a metacarpal 5 fracture was reported. All fractures healed uneventfully and metal removal was performed after a mean of 92 days (range 31 to 104). After a mean follow-up of 26 months (range 2 to 74), all patients had full range of movement and cosmetic results were described as good and satisfactory by all patients.
ESIN of the metacarpals is a safe, minimally invasive, and technically easy option in displaced fractures that warrant surgical intervention achieving excellent long-term results. Complications occurred when technical aspects to obtain stability were neglected or tendons and nerves of the hand had been injured. Stabilizing fractures of metacarpal 1 is technically challenging when compared with fractures of metacarpals 2 to 5.
Since 1987, psychosocial services have been a part of the primary care setting in Germany. In the framework of an eight-center national demonstration program, problems in the diagnosis and therapy of ...psychosocial problems and psychosomatic disorders were assessed. Methods to improve quality were also implemented.
General practitioners (n = 191) from six regions participated in the study. One thousand three hundred and forty-one treatment episodes of patients with predominantly psychosocial symptoms were documented. Differences between psychosocial strain, treatment, and outcome were determined by analyses of variance.
Anxiety (62%), depression (51%), and marital/family conflicts (44%) were the most frequent symptoms. Psychosocial treatment was offered more often to those patients who had the highest level of anxiety and depression. Patients with pain and without a psychological attribution to their illnesses were offered less psychosocial treatment and suffered worse results. Partners and family members were rarely integrated into therapy. The procedures employed to improve outcome were quality circles, family-oriented case conferences, consultation services, and collaborative groups.
These initial results are promising. A process of internal quality management has been initiated. Some of the physicians still resist documenting the data. Patients with somatic symptoms without psychological attribution may need special psychosocial interventions to improve their outcomes.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
We describe the case of a 16-year-old German male expatriate from Ghana who presented with obstipation, dysuria, dysaesthesia of the gluteal region and the lower limbs, bilateral plantar hypaesthesia ...and paraesthesia without pareses. A serum-cerebrospinal fluid (CSF) Schistosoma spp. specific antibody specificity index of 3.1 was considered highly suggestive of intrathecal synthesis of anti-Schistosoma spp. specific antibodies, although standardization of this procedure has not previously been described. Diagnosis was confirmed by detection of Schistosoma DNA in CSF by semi-quantitative real-time PCR at 100-fold concentration compared with serum. Accordingly the two diagnostic procedures, which have not previously been applied for routine diagnosis, appear to be useful for the diagnosis of neuroschistosomiasis. Clinical symptoms resolved following anthelmintic and anti-inflammatory therapy.
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