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Interference with particular spliceosome components, including small nuclear RNAs, cause reproducible uniquely distributed phenotypic and transcript-specific effects, making this an important category of disease-associated mutation. Our approach to differential expression analysis of minor intron-containing genes is applicable to other diseases involving altered transcriptome processing. ANN NEUROL 2017;81:68-78.

OBJECTIVE: Determine whether dexamethasone treatment added to salbutamol reduces time to readiness for discharge in patients with bronchiolitis and possible asthma. METHODS: We compared efficacy and safety of dexamethasone, 1 mg/kg, then 0.6 mg/kg for 4 more days, with placebo for acute bronchiolitis in patients with asthma risk, as determined by eczema or a family history of asthma in a first-degree relative. All patients received inhaled salbutamol. Time to readiness for discharge was the primary efficacy outcome. RESULTS: Two hundred previously healthy infants diagnosed with bronchiolitis, median age 3.5 months, were enrolled. Five placebo recipients needed admission to intensive care unit during infirmary treatment (P = .02). Among 100 dexamethasone recipients, geometric mean time to readiness for discharge was 18.6 hours (95% confidence interval [CI], 14.9 to 23.1 hours); among 90 control patients, 27.1 hours (95% CI, 21.8 to 33.8 hours). The ratio, 0.69 (95% CI, 0.51 to 0.93), revealed a mean 31% shortening of duration to readiness for discharge favoring dexamethasone (P = .015). Twenty-two dexamethasone and 19 control patients were readmitted to the short stay infirmary in the week after discharge (P = .9). No hospitalizations or side effects were reported during 7 days of surveillance. CONCLUSIONS: Dexamethasone with salbutamol shortened time to readiness for infirmary discharge during bronchiolitis episodes in patients with eczema or a family history of asthma in a first-degree relative. Infirmary and clinic visits in the subsequent week occurred similarly for the 2 groups.

Glutamine synthetase (GS) is ubiquitously expressed in mammalian organisms and is a key enzyme in nitrogen metabolism. It is the only known enzyme capable of synthesising glutamine, an amino acid with many critical roles in the human organism. A defect in GLUL, encoding for GS, leads to congenital systemic glutamine deficiency and has been described in three patients with epileptic encephalopathy. There is no established treatment for this condition.Here, we describe a therapeutic trial consisting of enteral and parenteral glutamine supplementation in a four year old patient with GS deficiency. The patient received increasing doses of glutamine up to 1020 mg/kg/day. The effect of this glutamine supplementation was monitored clinically, biochemically, and by studies of the electroencephalogram (EEG) as well as by brain magnetic resonance imaging and spectroscopy.Treatment was well tolerated and clinical monitoring showed improved alertness. Concentrations of plasma glutamine normalized while levels in cerebrospinal fluid increased but remained below the lower reference range. The EEG showed clear improvement and spectroscopy revealed increasing concentrations of glutamine and glutamate in brain tissue. Concomitantly, there was no worsening of pre-existing chronic hyperammonemia.In conclusion, supplementation of glutamine is a safe therapeutic option for inherited GS deficiency since it corrects the peripheral biochemical phenotype and partially also improves the central biochemical phenotype. There was some clinical improvement but the patient had a long standing severe encephalopathy. Earlier supplementation with glutamine might have prevented some of the neuronal damage.

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Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by hypotonia, progressive muscle weakness, and wasting. Onasemnogene abeparvovec (Zolgensma®) is a novel gene therapy medicine, FDA-approved in May 2019 for the treatment of SMA. This study aimed to describe Qatari experience with onasemnogene abeparvovec by reviewing the clinical outcomes of 9 SMA children (7 SMA type 1 and 2 with SMA type 2) aged 4‒23 months treated between November 2019 and July 2020. Children <2 years with 5q SMA with a bi-allelic mutation in the SMN1 gene were eligible for gene therapy. Liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin), platelet count, coagulation profile, troponin-I levels, and motor scores (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]), were regularly monitored following gene therapy. All patients experienced elevated AST or ALT, two experienced high prothrombin time, and one experienced elevated bilirubin; all of these patients were asymptomatic. Furthermore, one event of vomiting after infusion was reported in one patient. Significant improvements in CHOP INTEND scores were observed following therapy. This study describes the short-term outcomes and safety of onasemnogene abeparvovec, which is well tolerated and shows promise for early efficacy.

Children below the age of two demonstrated significantly higher percentages of abnormal imaging (59%), as did children presenting with status epilepticus (58%). Neuro-imaging should be considered in infants and those with focal or prolonged seizures. Neuro-imaging informed decision making in 6-8% of children.