A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway phospholipid biosynthesis.

Mutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine. Phosphatidylethanolamine is a glycerophospholipid that, together with phosphatidylcholine, constitutes more than half of the total phospholipids in eukaryotic cell membranes. We determined that the mutation defined dramatically reduces the enzymatic activity of EPT1, thereby hindering the final step in phosphatidylethanolamine synthesis. Additionally, due to central nervous system inaccessibility we undertook quantification of phosphatidylethanolamine levels and species in patient and control blood samples as an indication of liver phosphatidylethanolamine biosynthesis. Although this revealed alteration to levels of specific phosphatidylethanolamine fatty acyl species in patients, overall phosphatidylethanolamine levels were broadly unaffected indicating that in blood EPT1 inactivity may be compensated for, in part, via alternate biochemical pathways. These studies define the first human disorder arising due to defective CDP-ethanolamine biosynthesis and provide new insight into the role of Kennedy pathway components in human neurological function.

Guillain-Barré Syndrome Associated with SARS-CoV-2 in Two Pediatric Patients.

Guillain-Barré syndrome (GBS) is a recognised complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report two children with GBS associated with SARS-CoV-2 who presented to a tertiary centre in Muscat, Oman in 2021: The first patient was a three-month-old female infant who presented with bradypnea, encephalopathy, and generalised weakness that required mechanical ventilation. Polymerase chain reaction (PCR) testing of the nasopharyngeal swabs (NPS) was positive for SARS-CoV-2. She had axonal variant GBS based on a nerve conduction study, cerebrospinal fluid analysis, and neuroimaging findings. The second patient was a six-year-old girl with fever, vomiting, and diarrhea followed by ascending weakness who presented with quadriplegia and facial weakness. Subsequently, she developed respiratory muscle weakness and required mechanical ventilation. PCR testing of NPS was negative for SARS-Cov-2, however IgG serology analysis was positive. The clinical course of these two patients was rapidly progressive and both of them required mechanical ventilation. The patient with axonal variant GBS made an incomplete recovery.

Characterization of OXA-181, a carbapenem-hydrolyzing class D beta-lactamase from Klebsiella pneumoniae.

Klebsiella pneumoniae KP3 was isolated from a patient transferred from India to the Sultanate of Oman. K. pneumoniae KP3 was resistant to all ß-lactams, including carbapenems, and expressed the carbapenem-hydrolyzing ß-lactamase OXA-181, which differs from OXA-48 by four amino acid substitutions. Compared to OXA-48, OXA-181 possessed a very similar hydrolytic profile. The bla(OXA-181) gene was located on a 7.6-kb ColE-type plasmid and was linked to the insertion sequence ISEcp1. The ISEcp1-mediated one-ended transposition of bla(OXA-181) was also demonstrated.

NDM-1-producing Klebsiella pneumoniae isolated in the Sultanate of Oman.

OBJECTIVES: To analyse the mechanisms responsible for multidrug resistance in two carbapenem-resistant Klebsiella pneumoniae isolates recovered from patients hospitalized in Oman. METHODS: PCR and sequencing were used to search for ß-lactamase and 16S RNA methylase genes. Multilocus sequence typing was used to determine the sequence type (ST) of each isolate. Clonal relationships were evaluated by PFGE. RESULTS: Both isolates carried the bla(NDM-1) carbapenemase gene. Isolate 601 was recovered from a patient who was transferred from India, whereas isolate 419 was from an Omani patient who had not travelled abroad. The two isolates were clonally unrelated, and belonged to ST14 (isolate 601) and ST340 (isolate 419). In addition to NDM-1, the ST14 isolate expressed ß-lactamases CTX-M-15, SHV-28, OXA-1, OXA-9 and TEM-1, and the aminoglycoside resistance methylase ArmA. The ST340 isolate expressed ß-lactamases SHV-11, OXA-1 and ArmA. In both isolates, the bla(NDM-1) gene was located on plasmids that were of similar size (170 kb), but of different incompatibility groups. CONCLUSION: This is the first description of NDM-1 producers in the Arabian peninsula and in the Middle East.