Escobar Syndrome (Multiple Pterygium Syndrome) Associated with Thoracic Kyphoscoliosis,Lordoscoliosis, and Severe Restrictive Lung Disease: A Case Report

Background Escobar syndrome or multiple pterygium syndrome is characterized by a web across every flexion crease in the extremities, most notably the popliteal space. In addition, this syndrome is associated with two other structural anomalies: a vertical talus and congenital lordoscoliosis. We present a case report of a patient with Escobar syndrome who was initially managed conservatively and subsequently had severe and debilitating progression and respiratory decompensation ultimately requiring surgical intervention.Study Design Case report.Methods After preoperative evaluation by a pediatrician, pulmonologist, and otolaryngologist, the patient underwent one-stage anterior and posterior spinal fusion with instrumentation as well as multiple osteotomies, rib resections, and vertebrectomies.Results The patient’s postoperative course was complicated by wound necrosis requiring irrigation and debridement, a urinary tract infection, and a tracheostomy for persistent atelectasis. The patient eventually recovered from all complications. There were never any focal neurologic deficits. The patient had a 3-year follow-up with radiographically confirmed maintenance of correction. Fusion was obtained in the anterior and posterior segments. Clinically, the patient is able to stand upright, can participate in functional activities, and has not required any pain medication. The patient’s functional vital capacity improved from 23% predicted preoperatively to 60% predicted postoperatively.Conclusions Patients with severe spinal deformity secondary to Escobar syndrome can be successfully treated surgically. We propose early surgical intervention in this group to prevent curve progression, restrictive lung disease, and the need for complex salvage procedures.     

Reduction of hepatic and adipose tissue glucocorticoid receptor expression with antisense oligonucleotides improves hyperglycemia and hyperlipidemia in diabetic rodents without causing systemic glucocorticoid antagonism

Glucocorticoids (GCs) increase hepatic gluconeogenesis and play an important role in the regulation of hepatic glucose output. Whereas systemic GC inhibition can alleviate hyperglycemia in rodents and humans, it results in adrenal insufficiency and stimulation of the hypothalamic-pituitary-adrenal axis. In the present study, we used optimized antisense oligonucleotides (ASOs) to cause selective reduction of the glucocorticoid receptor (GCCR) in liver and white adipose tissue (WAT) and evaluated the resultant changes in glucose and lipid metabolism in several rodent models of diabetes. Treatment of ob/ob mice with GCCR ASOs for 4 weeks resulted in approximately 75 and approximately 40% reduction in GCCR mRNA expression in liver and WAT, respectively. This was accompanied by approximately 65% decrease in fed and approximately 30% decrease in fasted glucose levels, a 60% decrease in plasma insulin concentration, and approximately 20 and 35% decrease in plasma resistin and tumor necrosis factor-alpha levels, respectively. Furthermore, GCCR ASO reduced hepatic glucose production and inhibited hepatic gluconeogenesis in liver slices from basal and dexamethasone-treated animals. In db/db mice, a similar reduction in GCCR expression caused approximately 40% decrease in fed and fasted glucose levels and approximately 50% reduction in plasma triglycerides. In ZDF and high-fat diet-fed streptozotocin-treated (HFD-STZ) rats, GCCR ASO treatment caused approximately 60% reduction in GCCR expression in the liver and WAT, which was accompanied by a 40-70% decrease in fasted glucose levels and a robust reduction in plasma triglyceride, cholesterol, and free fatty acids. No change in circulating corticosterone levels was seen in any model after GCCR ASO treatment. To further demonstrate that GCCR ASO does not cause systemic GC antagonism, normal Sprague-Dawley rats were challenged with dexamethasone after treating with GCCR ASO. Dexamethasone increased the expression of GC-responsive genes such as PEPCK in the liver and decreased circulating lymphocytes. GCCR ASO treatment completely inhibited the increase in dexamethasone-induced PEPCK expression in the liver without causing any change in the dexamethasone-induced lymphopenia. These studies demonstrate that tissue-selective GCCR antagonism with ASOs may be a viable therapeutic strategy for the treatment of the metabolic syndrome.     

Relationship of a leukemia-associated antigen to the presence of lymphoblasts in the peripheral blood in children with acute lymphocytic leukemia

Peripheral blood samples from 57 children with newly diagnosed E- rosette-negative, surface-immunoglobulin negative acute lymphocytic leukemia (ALL) were studied for the presence of a leukemia-associated antigen (ALLA). Ficoll-Hypaque separated cells were tested using a rabbit antiserum to human null lymphoblasts and an indirect immunofluorescent assay. The percentage of ALLA-positive cells were compared to the percentage of lymphoblasts determined by differential counts of a Wright-Giemsa-stained smear of a concurrently obtained peripheral blood sample. The mean ratio of percentage of lymphoblasts to percentage of ALLA-positive cells was 0.90. However, in 13 patients, the ratio of percent of ALLA-positive cells to percent of lymphoblasts was equal to or greater than 2:1. In the blood of 6 additional children (5 newly diagnosed, 1 relapsed patient) in whom no morphologically identifiable lymphoblasts were detected. ALLA-positive cells were present (7%-49%). These results indicate that testing for ALLA-positive cells in a sensitive technique for detection of leukemic cells in children with ALLA-positive ALL.     

Chronic valproate administration produces hepatic dysfunction and may delay brain maturation in infant mice

Infant mice (2 to 4 days old) received valproate (100 or 200 mg per kilogram body weight) subcutaneously once daily for 5 days. Both dosages decreased plasma beta-hydroxybutyrate levels to about one-third of the control value, in the face of normal free fatty acid and glycerol levels. At 200 mg per kilogram of valproate, there were significant decreases in brain weight and brain K content. Both doses produced metabolite changes in brain compatible with a reduced metabolic flux through the glycolytic pathway and the citric acid cycle. Valproate reduced brain aspartate but did not increase brain GABA levels in infant mice. At 200 mg per kilogram of valproate, brain glutamate decreased and taurine levels increased. Two hundred milligrams per kilogram of valproate caused a profound reduction of liver glycogen stores. The apparent decrease in cerebral metabolic rate, reduced glutamate and aspartate, and increased levels of taurine in brain may relate to the anticonvulsant action of valproate. Together with the decreased brain weight and K content, the findings are also compatible with maturational delay. Decreased ketonemia and liver glycogen content may relate to the hepatic toxicity associated with valproate administration in infants and children.