Knowledge, attitudes and practices of healthcare workers during the early COVID-19 pandemic in a main, academic tertiary care centre in Saudi Arabia.

As the Middle East respiratory syndrome coronavirus (MERS-CoV) continues to occur in small outbreaks in Saudi Arabia, we aimed to assess the knowledge, attitudes and intended practices of healthcare workers (HCWs) during the early stage of the COVID-19 pandemic and compare worry levels with previous findings during the MERS-CoV outbreak in 2015. We sent an adapted version of our previously published MERS-CoV questionnaire to the same cohort of HCWs at a tertiary hospital in Saudi Arabia. About 40% of our sample had previous experience with confirmed or suspected MERS-CoV patients, and those had a significantly higher knowledge score (13.16 ± 2.02 vs. 12.58 ± 2.27, P = 0.002) and higher adherence to protective hygienic practices (2.95 ± 0.80 vs. 2.74 ± 0.92, P = 0.003). The knowledge scores on COVID-19 were higher in the current cohort than the previous MERS-CoV outbreak cohort (68% vs. 79.7%, P < 0.001). HCWs from the current cohort who felt greater anxiety from COVID-19 compared to MERS-CoV were less likely to have been exposed to MERS-CoV infected/suspected cases (odds ratio (OR) = 0.646, P = 0.042) and were less likely to have attended the hospital awareness campaign on COVID-19 (OR = 0.654, P = 0.035). We concluded that previous experience with MERS-CoV was associated with increased knowledge and adherence to protective hygienic practices, and reduction of anxiety towards COVID-19.

MRI Spectrum of Brain Involvement in Sphingosine-1-Phosphate Lyase Insufficiency Syndrome.

SGPL1 encodes sphingosine-1-phosphate lyase, the final enzyme of sphingolipid metabolism. In 2017, a condition featuring steroid-resistant nephrotic syndrome and/or adrenal insufficiency associated with pathogenic SGPL1 variants was reported. In addition to the main features of the disease, patients often exhibit a range of neurologic deficits. In a handful of cases, brain imaging results were described. However, high-quality imaging results and a systematic analysis of brain MR imaging findings associated with the condition are lacking. In this study, MR images from 4 new patients and additional published case reports were reviewed by a pediatric neuroradiologist. Analysis reveals recurring patterns of features in affected patients, including isolated callosal dysgenesis and prominent involvement of the globus pallidus, thalamus, and dentate nucleus, with progressive atrophy and worsening of brain lesions. MR imaging findings of abnormal deep gray nuclei, microcephaly, or callosal dysgenesis in an infant or young child exhibiting other typical clinical features of sphingosine-1-phosphate lyase insufficiency syndrome should trigger prompt genetic testing for SGPL1 mutations.

Successful Treatment of Recurrent Focal Segmental Glomerulosclerosis After Transplantation in Children: A Single-Center Experience.

OBJECTIVE: We aim to report our experience managing cases of recurrent focal segmental glomerulosclerosis (FSGS) in a group of pediatric renal transplant recipients. METHODS: This study was a retrospective chart review of pediatric patients who had their first kidney transplant at King Faisal Specialist Hospital & Research Center between 2014 and 2016. RESULTS: We reviewed the files of 6 patients, 3 of whom were male. The median age of the children was 2.75 years (range, 2-4 years) at disease onset, with an average time of progression to end-stage renal disease of 19 months (range, 8-30 months). Five of the patients received a living related donor transplant, and 1 received a living nonrelated donor transplant. Patients had FSGS recurrence at varying intervals (1 to 3 days) post transplant. All cases had plasmapheresis prior to receiving abatacept or rituximab. The therapeutic strategy in 4 patients involved switching tacrolimus to cyclosporine. A complete response was observed in 5 of the 6 patients (83.3%), and treatment was well tolerated in 5 patients. Patient 1 had severe oliguria and required intermittent hemodialysis during the first 3 weeks post transplant. He showed minimal response to the therapeutic plasma exchange and rituximab and was subsequently treated with abatacept. However, he died 8 months post transplant of pneumonia and sepsis. CONCLUSION: Rituximab and switching tacrolimus to cyclosporine, in conjunction with plasmapheresis, appeared to be effective and safe in children with recurrent FSGS. Conversely, abatacept did not appear to provide clinical benefit.

Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield.

Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.