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ABSTRACT Background Congenital disorders of glycosylation (CDG) are a group of neurometabolic diseases that result from genetic defects in the glycosylation of proteins and/or lipids. Multiple pathogenic genes contribute to the varying reported phenotypes of individuals with CDG‐1 syndromes, most of which are inherited as autosomal recessive traits, although X‐linked inheritance has also been reported. Pathogenic variants in the asparagine‐linked glycosylation 13 homolog (ALG13) gene have been implicated in the aetiology of developmental and epileptic encephalopathy (DEE) 36 (OMIM:*300776, DEE36). The NM_001099922.3:c.320A>G; p.(Asn107Ser) variant is the most frequently described pathogenic variant in ALG13, with 59 females and 2 males with this variant reported to date. Methods We report on a male with a de novo, hemizygous variant in ALG13: c.320A>G; p.(Asn107Ser), whose phenotype resembles that of two previously reported males with the same variant. Results All three males have a de novo mutation, infantile spasms, DEE, drug‐resistant epilepsy, intellectual disability, dysmorphic findings, recurrent infections, skeletal anomalies, brain abnormalities and a movement disorder: a phenotype not consistently reported in males with other pathogenic variants in ALG13. Conclusion The similarity of phenotype in the three males with the c.320A>G variant in ALG13, suggests a possible genotype–phenotype correlation.

OBJECTIVES:The United States National Institute for Occupational Safety and Health (NIOSH) is developing a protocol to assess the containment performance of closed system transfer devices (CSTDs) when used for drug preparation (task 1) and administration (task 2) and published a draft protocol in September 2016. Nine possible surrogates were proposed by NIOSH for use in the testing. The objectives of this study were to: (A) select the most appropriate surrogate; (B) validate the NIOSH protocol using this surrogate; and (C) determine the containment performance of four commercial CSTDs as compared with an open system of needle and syringe using the validated NIOSH protocol. METHODS:2-Phenoxyethanol (2-POE) was selected as a surrogate based on its water solubility, Henry's volatility constant, detectability by mass spectrometry, and non-toxicity. Standard analytical validation methods including system suitability, limit of detection (LOD), and limit of quantitation (LOQ) as well as system cleaning validation were performed. The amount of 2-POE released when the CSTDs were manipulated according to two tasks defined by NIOSH was determined using mass spectrometry coupled to thermal desorption and gas chromatography. This approach allows sensitivity of detection below 1 part per billion (ppb). Equashield, Tevadaptor (OnGuard), PhaSeal, and ChemoClave were assessed according to manufacturers' instructions for use. RESULTS:2-POE was tested and validated for suitability of use within the NIOSH protocol. A simple and efficient cleaning protocol achieved consistently low background values, with an average value, based on 85 measurements, of 0.12 ppb with a 95% confidence interval (CI) of ±0.16 ppb. This gives an LOD for the tests of 0.35 ppb and an LOQ of 0.88 ppb. The Equashield, Tevadaptor (OnGuard), and PhaSeal devices all showed average releases, based on 10 measurements from five tests, that were less than the LOQ (i.e. < 0.88 ppb), while the ChemoClave Vial Shield with Spinning Spiros showed average releases of 2.9±2.3 ppb and 7.5±17.9 ppb for NIOSH tasks 1 and 2 respectively at the 95% confidence level. The open system of needle and syringe showed releases, based on two measurements from a single test, of 4.2±2.2 ppb and 5.1±1.7 ppb for NIOSH tasks 1 and 2 respectively at the 95% confidence level. CONCLUSIONS:2-POE proved to be an ideal surrogate for testing of CSTDs using the NIOSH protocol. We propose that a CSTD can be qualified using the NIOSH testing approach if the experimental LOQ is less than 1 ppb and the release values are below the LOQ. Equashield, Tevadaptor (OnGuard), and PhaSeal meet these acceptance criteria and can therefore all be qualified as CSTDs, but the ChemoClave system does not and so would not qualify as a CSTD.