Utility of next generation sequencing in paediatric neurological disorders: experience from South Africa.

Next generation sequencing (NGS)-based tests have become routine first-line investigative modalities in paediatric neurology clinics in many high-income countries (HICs). Studies from these countries show that these tests are both cost-effective and reliable in diagnosing many complex childhood neurological diseases. However, NGS-based testing in low-and middle-income countries (LMICs) is limited due to affordability constraints. The primary objective of this study was to evaluate the diagnostic yield and impact of targeted gene panel sequencing in a selected paediatric cohort attending a tertiary paediatric neurology clinic in the Western Cape Province of South Africa. This retrospective study included 124 consecutive paediatric patients with neurological disease, aged 6 weeks to 17 years, referred for NGS-based multi-gene panel testing over a 41-month period. Twenty-four different disease group-specific panels were utilized. A caregiver experience questionnaire was administered when a pathogenic variant was identified. The overall study diagnostic yield (DY) was 45% (56/124 patients). The diagnostic yield in this study is similar to previously reported paediatric cohorts in HICs. The high yields for neuromuscular disorders (52%) and early epileptic encephalopathies (41%) suggest that NGS-based panels may be more cost-effective as first-line testing in well-defined phenotypes. The latter finding argues for early inclusion of all children with developmental epileptic encephalopathies (DEE), as early diagnosis leads to better treatment and avoidance of unnecessary investigations.

Adar-associated Aicardi Goutières syndrome in a child with bilateral striatal necrosis and recurrent episodes of transaminitis.

Aicardi-Goutières syndrome (AGS) refers to a group of genetic diseases characterised by severe inflammatory encephalopathy that usually present within the first year of life, resulting in progressive loss of cognition, spasticity, dystonia and motor disability. Pathogenic variants in the adenosine deaminase acting on RNA (Adar) enzyme have been linked to AGS type 6 (AGS6, Online Mendelian Inheritance in Man (OMIM) 615010). In knockout mouse models, loss of Adar activates the interferon (IFN) pathway and causes autoimmune pathogenesis in the brain or liver. Bilateral striatal necrosis (BSN) has previously been reported in case series of children with biallelic pathogenic variants in Adar We describe a unique, previously unreported case of a child with AGS6, with clinical manifestations of BSN and recurrent transient episodes of transaminitis. The case highlights the importance of Adar in protecting the brain and liver from IFN-induced inflammation. Adar-related disease should therefore be considered in the differential diagnosis of BSN accompanied by recurrent episodes of transaminitis.

Giant cerebral tuberculoma mimicking a high-grade tumour in a child.

We present an 11-year-old girl who manifested with unprovoked right-sided focal motor seizures. CT revealed a large lobulated hypodense mass in the left temporoparietal lobe, with perilesional oedema and postcontrast peripheral enhancement. Diagnostic uncertainty resulted in further neuroimaging, which included MRI with modalities including diffusion-weighted imaging, perfusion imaging, as well as spectroscopy. We discuss the radiological features of the lesion, which steered us in the direction of an infective cause. Definitive diagnosis was achieved by brain needle biopsy, which demonstrated necrotising granulomatous inflammation indicative of tuberculous infection on histology. In addition, GeneXpert yielded a positive result. We believe this unique case highlights the diagnostic dilemma clinicians face in differentiating ring-enhancing lesions on neuroimaging in tuberculosis-endemic regions. It also highlights the potential benefit of a brain needle biopsy (histology and GeneXpert) in cases of uncertainty.

Healthcare-Associated Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in a Neonatal Unit: The Importance of Universal Masking, Hand Hygiene, and Symptom Screening in Containment.

Following exposure to a healthcare worker with an influenza-like illness, 2 preterm neonates and 6 staff members developed symptoms and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This neonatal unit coronavirus disease 2019 outbreak occurred prior to the implementation of universal masking and symptom screening policies. Both neonates and all staff recovered, with no further healthcare-associated SARS-CoV-2 transmission following the implementation of effective outbreak containment measures.