Larson K.E.,University of South Dakota |
Carrillo-Marquez M.,Sanford Childrens Specialty Clinic |
Carrillo-Marquez M.,University of South Dakota
Journal of AAPOS | Year: 2015
We present a case of endogenous endophthalmitis in a 13-year-old boy with methicillin-resistant Staphylococcus aureus sepsis. The patient underwent magnetic resonance imaging of the brain after intermittent anisocoria was noted on examination, leading to a diagnosis of endophthalmitis with a chorodial abscess. © 2015 American Association for Pediatric Ophthalmology and Strabismus.
Peters S.,Sanford Childrens Specialty Clinic |
Peters S.,South Dakota State University |
van Gilder D.,South Dakota State University |
Dvoracek K.,University of Nebraska Medical Center |
Hegge K.A.,Sanford Medical Center
Clinical Medicine Insights: Therapeutics | Year: 2011
Phenylketonuria (PKU) is an autosomal recessive disorder related to a deficiency in the enzyme phenylalanine hydroxylase (PAH), which converts phenylalanine to tyrosine. As a result, phenylalanine can accumulate in the bloodstream, potentially leading to severe neurologic sequelae. Traditionally, PKU management involves strict dietary phenylalanine restriction, although adherence to this diet is suboptimal, necessitating improved therapeutic options. Sapropterin (Kuvan®) is a synthetic form of tetrahydrobioterin (BH4), a cofactor for PAH, and offers promise for patients with residual enzyme production. In four pivotal phase 2 and 3 trials, as well as several smaller trials, sapropterin has demonstrated significantly improved plasma phenylalanine concentrations in patients with BH4-responsive PKU. Furthermore, data exist to support reduced dependence on a restricted phenylalanine diet. Sapropterin has a favorable safety profile, but further studies are warranted to evaluate its long-term effects. Sapropterin represents a significant advancement in PKU management, and its clinical role may continue to evolve as more data become available and clinicians gain experience with this novel pharmacologic agent. © the author(s), publisher and licensee Libertas Academica Ltd.
Bernardo V.,St. Louis College of Pharmacy |
Shelso J.,Sanford Childrens Specialty Clinic |
Ribeiro R.C.,St Jude Childrens Research Hospital
Journal of Pediatric Hematology/Oncology | Year: 2014
We report a 4-month-old male presenting with hypocalcemia, hyperleukocytosis, and newly diagnosed acute myeloid leukemia. He received chemical leukoreduction through low-dosed cytarabine, with appropriate decrease in his white blood cell count and development of subsequent symptomatic hypocalcemia, which did not normalize until the underlying vitamin D deficiency was addressed. A single dose of cholecalciferol raised the serum calcium concentration to an appropriate level within 48 hours. For infants with newly diagnosed leukemia and prolonged hypocalcemia, vitamin D deficiency should be considered in the differential diagnosis and managed appropriately. Copyright © 2013 by Lippincott Williams & Wilkins.
Jensen M.,Sanford Childrens Specialty Clinic |
Abu-El-Haija M.,Cincinnati Childrens Hospital Medical Center |
Bishop W.,University of Iowa |
Rahhal R.M.,University of Iowa
Journal of Pediatric Gastroenterology and Nutrition | Year: 2015
Objectives: Oral high-dose repletion vitamin D therapy, also known as stoss therapy, can be effective in the treatment of nutritional vitamin D deficiency rickets in infants and young children without liver disease and in patients with cystic fibrosis. There is no literature about this approach in infants with new-onset cholestasis. Methods: This was a retrospective chart review of infants with cholestasis from March 2010 to March 2012 at a pediatric tertiary care center. Four cases satisfied the inclusion criteria, and were described in detail. Results: All of the patients received oral high-dose repletion therapy with ergocalciferol (vitamin D2) 300,000 IU daily for 2 to 3 days. Follow-up vitamin D levels approximately 4 weeks later showed failure to achieve sufficiency levels (>20 ng/dL) in any patient. Conclusions: Unlike infants without liver disease, use of oral high-dose repletion therapy may not be adequate as treatment of vitamin D deficiency in the setting of cholestasis. Copyright © 2015 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
Snijders Blok L.,Radboud University Nijmegen |
Madsen E.,Duke University |
Juusola J.,GeneDx |
Gilissen C.,Radboud University Nijmegen |
And 84 more authors.
American Journal of Human Genetics | Year: 2015
Intellectual disability (ID) affects approximately 1%-3% of humans with a gender bias toward males. Previous studies have identified mutations in more than 100 genes on the X chromosome in males with ID, but there is less evidence for de novo mutations on the X chromosome causing ID in females. In this study we present 35 unique deleterious de novo mutations in DDX3X identified by whole exome sequencing in 38 females with ID and various other features including hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Based on our findings, mutations in DDX3X are one of the more common causes of ID, accounting for 1%-3% of unexplained ID in females. Although no de novo DDX3X mutations were identified in males, we present three families with segregating missense mutations in DDX3X, suggestive of an X-linked recessive inheritance pattern. In these families, all males with the DDX3X variant had ID, whereas carrier females were unaffected. To explore the pathogenic mechanisms accounting for the differences in disease transmission and phenotype between affected females and affected males with DDX3X missense variants, we used canonical Wnt defects in zebrafish as a surrogate measure of DDX3X function in vivo. We demonstrate a consistent loss-of-function effect of all tested de novo mutations on the Wnt pathway, and we further show a differential effect by gender. The differential activity possibly reflects a dose-dependent effect of DDX3X expression in the context of functional mosaic females versus one-copy males, which reflects the complex biological nature of DDX3X mutations. © 2015 The American Society of Human Genetics.