Mutations in the gene SLC19A3 result in thiamine metabolism dysfunction syndrome 2, also known as biotin-thiamine-responsive basal ganglia disease (BTBGD). This neurometabolic disease typically presents in early childhood with progressive neurodegeneration, including confusion, seizures, and dysphagia, advancing to coma and death. Treatment is possible via supplement of biotin and/or thiamine, with early treatment resulting in significant lifelong improvements. Here we report two siblings who received a refined diagnosis of BTBGD following whole-genome sequencing. Both children inherited compound heterozygous mutations from unaffected parents; a missense single-nucleotide variant (p.G23V) in the first transmembrane domain of the protein, and a 4808-bp deletion in exon 1 encompassing the 5′ UTR and minimal promoter region. This deletion is the smallest promoter deletion reported to date, further defining the minimal promoter region of SLC19A3. Unfortunately, one of the siblings died prior to diagnosis, but the other is showing significant improvement after commencement of therapy. This case demonstrates the power of whole-genome sequencing for the identification of structural variants and subsequent diagnosis of rare neurodevelopmental disorders.
Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in a vulvo-vaginitis and altered vaginal discharge in symptomatic women. Since its introduction in the 1960 s, metronidazole has been the first-line drug for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or reinfection, although metronidazole resistance has previously been documented. Sensitivity testing is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. This case looks at a patient with refractory disease over an 18-month period, where intravenous infusion of metronidazole resulted in cure after multiple previous therapy failures. There is limited evidence to endorse the use of intravenous metronidazole, and this case report provides further support for its efficacy.
Biodiversity compensation policies have emerged around the world to address the ecological harms of infrastructure expansion, but they have historically experienced weak compliance. The English government is introducing a requirement that all new infrastructure developments demonstrate they achieve a Biodiversity Net Gain (BNG). Previous research has highlighted governance gaps that risk undermining the policy’s ecological outcomes, as well as exploring the risks caused by fundamental capacity constraints in regulators, but the magnitude of their effects on the policy’s potential impacts on biodiversity remains unexplored. We collated BNG information from all new major developments across six early adopter councils from 2020-2022. We quantified the proportion of the biodiversity outcomes promised under BNG which are at risk of non-compliance, explored the variation in strategies that developments use to meet their biodiversity liabilities, and quantified the occurrence of simple errors in the biodiversity metric calculations submitted by project proponents. Large developments and energy infrastructure were more likely to meet their liability within their own development footprint, and small developments more likely to purchase offsets. We estimate that 27% of all biodiversity units fall within governance gaps that expose them to a high risk of non-compliance. Should these units instead be delivered through the off-site biodiversity offsetting market – which is associated with relatively more robust governance mechanisms – we estimate that the demand for offsets could rise by a factor of four, increasing the financial contributions generated by BNG for conservation activities on private land. Lastly, we find that 21% of applications contained conspicuous errors in their BNG calculations, half of which have already been accepted by councils, hinting at under-resourcing in councils assessing developments. Our findings demonstrate that resourcing and governance shortfalls risk undermining the policy’s effectiveness at halting biodiversity loss and require addressing to ensure the policy benefits nature.
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