Metabolic investigations prevent liver transplantation in two young children with citrullinemia type I

Acute liver failure may be caused by a variety of disorders including inborn errors of metabolism. In those cases, rapid metabolic investigations and adequate treatment may avoid the need for liver transplantation. We report two patients who presented with acute liver failure and were referred to our center for liver transplantation work-up. Urgent metabolic investigations revealed citrullinemia type I. Treatment for citrullinemia type I avoided the need for liver transplantation. Acute liver failure as a presentation of citrullinemia type I has not previously been reported in young children. Although acute liver failure has occasionally been described in other urea cycle disorders, these disorders may be underestimated as a cause. Timely diagnosis and treatment of these disorders may avoid liver transplantation and improve clinical outcome. Therefore, urea cycle disorders should be included in the differential diagnosis in young children presenting with acute liver failure

The TURis System for Transurethral Resection of the Prostate: A NICE Medical Technology Guidance

The transurethral resection in saline (TURis) system was notified by the company Olympus Medical to the National Institute of Health and Care Excellence’s (NICE’s) Medical Technologies Evaluation Programme. Following selection for medical technologies guidance, the company developed a submission of clinical and economic evidence for evaluation. TURis is a bipolar surgical system for treating men with lower urinary tract symptoms due to benign prostatic enlargement. The comparator is any monopolar transurethral resection of the prostate (mTURP) system. Cedar, a collaboration between Cardiff and Vale University Health Board, Cardiff University and Swansea University in the UK, acted as an External Assessment Centre (EAC) for NICE to independently critique the company’s submission of evidence. Eight randomised trials provided evidence for TURis, demonstrating efficacy equivalent to that of mTURP for improvement of symptoms. The company presented meta-analyses of key outcome measures, and the EAC made methodological modifications in response to the heterogeneity of the trial data. The EAC analysis found that TURis substantially reduced the relative risks of transurethral resection syndrome (relative risk 0.18 [95 % confidence interval 0.05–0.62]) and blood transfusion (relative risk 0.35 [95 % confidence interval 0.19–0.65]). The company provided a de novo economic model comparing TURis with mTURP. The EAC critiqued the model methodology and made modifications. This found TURis to be cost saving at £70.55 per case for existing Olympus customers and cost incurring at £19.80 per case for non-Olympus customers. When an additional scenario based on the only available data on readmission (due to any cause) from a single trial was modelled, the estimated cost saving per case was £375.02 for existing users of Olympus electrosurgery equipment and £284.66 per case when new Olympus equipment would need to be purchased. Meta-analysis of eight randomised trials showed that TURis is associated with a statistically significantly reduced risk of transurethral resection syndrome and a reduced need for blood transfusion—two factors that may drive cost saving for the National Health Service. The clinical data are equivocal as to whether TURis shortens the hospital stay. Limited data from a single study suggest that TURis may reduce the rate of readmission after surgery. The NICE guidance supports adoption of the TURis technology for performing transurethral resection of the prostate in men with lower urinary tract symptoms due to benign prostatic enlargemen

Clinical characterization of Collagen XII-related disease caused by biallelic <em>COL12A1</em> variants

\ua9 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. Objective: While there have been several reports of patients with dominantly acting COL12A1 variants, few cases of the more severe recessive Collagen XII-related disorders have previously been documented. Methods: We present detailed clinical, immunocytochemical, and imaging data on eight additional patients from seven families with biallelic pathogenic variants in COL12A1. Results: All patients presented with a consistent constellation of congenital onset clinical features: hypotonia, dysmorphic features, most notably gingival hypertrophy, prominent distal joint hyperlaxity, with co-occurring contractures of large joints, and variable muscle involvement, evident both clinically and on muscle imaging. Five patients presented with a severe congenital phenotype manifesting with profound weakness, significantly delayed or minimal attainment of motor milestones, respiratory insufficiency, and feeding difficulties. Three patients presented with mild-to-moderate muscle weakness and delayed milestones but were able to achieve independent ambulation. Patients were found to have biallelic loss-of-function COL12A1 variants, except for one family (p.I1393Ffs*11/p.A1110D). Consistent with the variable clinical spectrum, in vitro immunocytochemistry analysis in fibroblasts ranged from complete absence of Collagen XII expression in a patient with severe disease, to a mild reduction in a patient with milder disease. Interpretation: Here we characterize the clinical presentation, muscle imaging, and dermal fibroblast immunostaining findings associated with biallelic variants in COL12A1, further establishing COL12A1 as a recessive myopathic Ehlers–Danlos syndrome (mEDS) gene, and expanding the clinical spectrum to include a milder EDS phenotype

Abnormal neurological features predict poor survival and should preclude liver transplantation in patients with deoxyguanosine kinase deficiency.

Deoxyguanosine kinase (DGUOK) deficiency is the commonest type of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this article, we evaluate predictors of survival and therapeutic options in patients with DGUOK deficiency. A systematic search of MEDLINE, LILAC, and SCIELO was carried out to identify peer-reviewed clinical trials, randomized controlled trials, meta-analyses, and other studies with clinical pertinence. DGUOK deficiency was searched with the terms dGK, DGUOK, mitochondrial DNA depletion, mtDNA, and hepatocerebral. Bibliographies of identified articles were reviewed for additional references. Thirteen identified studies met the inclusion criteria and were used in this study. The analysis revealed that DGUOK deficiency is associated with a variable clinical phenotype. Long-term survival is best predicted by the absence of profound hypotonia, significant psychomotor retardation, or nystagmus. In the presence of these features, there is increased mortality, and liver transplantation does not confer increased survival. In summary, liver transplantation appears to be futile in the presence of specific neurological signs or symptoms in patients affected with DGUOK deficiency. Conversely, in the absence of these neurological features, liver transplantation may be considered a potential treatment