We report biallelic missense and frameshift pathogenic variants in the gene encoding human nucleoporin NUP214 causing acute febrile encephalopathy. Clinical symptoms include neurodevelopmental regression, seizures, myoclonic jerks, progressive microcephaly, and cerebellar atrophy. NUP214 and NUP88 protein levels were reduced in primary skin fibroblasts derived from affected individuals, while the total number and density of nuclear pore complexes remained normal. Nuclear transport assays exhibited defects in the classical protein import and mRNA export pathways in affected cells. Direct surface imaging of fibroblast nuclei by scanning electron microscopy revealed a large increase in the presence of central particles (known as ''plugs'') in the nuclear pore channels of affected cells. This observation suggests that large transport cargoes may be delayed in passage through the nuclear pore channel, affecting its selective barrier function. Exposure of fibroblasts from affected individuals to heat shock resulted in a marked delay in their stress response, followed by a surge in apoptotic cell death. This suggests a mechanistic link between decreased cell survival in cell culture and severe fever-induced brain damage in affected individuals. Our study provides evidence by direct imaging at the single nuclear pore level of functional changes linked to a human disease.

Introduction: Postoperative hypocalcemia is frequent after total thyroidectomy. The role of preoperative vitamin D levels in the pathogenesis of this condition has not been studied under the most current guidelines for evaluation of the role of vitamin D in calcium homeostasis. We hypothesized that patients with preoperative vitamin D deficiency are more likely to suffer from postoperative hypocalcemia, thereby requiring prolonged hospitalization. Methods: A retrospective chart review of patients undergoing total thyroidectomy at the University of New Mexico Hospital between 2005 and 2014 was performed. Patients who underwent parathyroidectomy were excluded. The study included 30 patients who had a 25-hydroxyvitamin D levels obtained within 12 months before surgery. Results: 12 patients with vitamin D deficiency (VDD; 25-hydroxyvitamin D ≤ 20 ng/ml) were compared to 18 patients without vitamin D deficiency (Non-VDD; 25-hydroxyvitamin D > 20 ng/ml). The mean nadir postoperative ionized calcium concentration was lower in the VDD group (0.99±0.10 vs. 1.06±0.06 mmol/l, p=0.04) (Ref Range = 1.15–1.27 mmol/l), as was the postoperative concentration of phosphorus (3.48±0.60 vs. 4.17±0.84 mg/dl, p=0.03). VDD patients had a longer length of stay (4.3±4.4 vs. 1.7±1.5 days, p=0.03). Three patients in the VDD group required intravenous calcium for treatment of symptomatic hypocalcemia, but none of the Non-VDD patients required this intervention (p=0.054). Conclusions: Preoperative vitamin D deficiency is associated with an increased risk of postoperative hypocalcemia and a prolonged length of stay in patients undergoing total thyroidectomy. Vitamin D replacement before thyroidectomy may improve postsurgical outcomes in vitamin D deficient patients.

A 37-year-old man with AIDS presented with altered mental status four weeks after stopping his medications for Mycobacterium avium-intracellulare (MAI). He had low CD4 cell count and severe hypercalcemia. Bone marrow biopsy revealed bone marrow infiltration by granulomas positive for acid-fast bacilli and cultures grew MAI. His hypercalcemia continued to worsen with the initiation of MAI therapy but we were able to treat it successfully with pamidronate and calcitonin.

SUMMARYA 47-year-old woman presented with left nipple itch and discomfort. On physical examination she was found to have a 7 mm lesion. She underwent bilateral mammography and bilateral breast ultrasound which were normal. A punch biopsy of the lesion was performed in the office and the specimen submitted to pathology. Histopathological examination showed ectatic vascular spaces lined by flattened, cytologically bland endothelial cells dissecting the dermal collagen. Evident lymphatic valves were present within the vascular spaces confirming that the vessels were lymphatic in nature. The diagnosis of acquired progressive lymphangioma (benign lymphangioendothelioma) was rendered. BACKGROUND

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