Time filter

Source Type

Oklahoma City, OK, United States

Peck D.S.,University of Missouri | Atherton A.M.,Section of Genetics | Manwaring L.P.,Washington University in St. Louis | Christensen K.M.,Cardinal Glennon Childrens Medical Center | And 2 more authors.
Genetics in Medicine | Year: 2015

Fabry disease is a pan-ethnic, progressive, X-linked genetic disorder that commonly presents in childhood and is caused by deficient activity of the lysosomal enzyme alpha-galactosidaseA (α-gal A). Symptoms of Fabry disease in the pediatric population are well described for patients over five years of age; however, data are limited for infancy and early childhood. The purpose of this article is to delineate the age of detection for specific Fabry symptoms in early childhood.Methods:A systematic retrospective analysis of PubMed indexed, peer-reviewed publications and case reports in the pediatric Fabry population was performed to review symptoms in patients reported before 5 years of age.Results:The most frequently reported symptom in all age groups under 5 years was acroparesthesias/neuropathic pain, reported in 9 children, ranging in age from 2.0-4.0 years. Also notable is the frequency of gastrointestinal issues reported in 6 children aged 1.0-4.1 years of age.Conclusion:This article finds clear evidence that symptoms can occur in early childhood, before age 5 years. Given early presenting symptoms and the ability to monitor these disease hallmarks, a timely referral to a medical geneticist or other specialty clinician experienced in managing children with Fabry disease is strongly indicated. © American College of Medical Genetics and Genomics. Source

Tang M.,University of Utah | Odejinmi S.I.,University of Utah | Vankayalapati H.,University of Utah | Wierenga K.J.,Section of Genetics | Lai K.,University of Utah
Molecular Genetics and Metabolism | Year: 2012

Classic Galactosemia is an autosomal recessive disorder caused by the deficiency of galactose-1-phosphate uridylyltransferase (GALT), one of the key enzymes in the Leloir pathway of galactose metabolism. While the neonatal morbidity and mortality of the disease are now mostly prevented by newborn screening and galactose restriction, long-term outcome for older children and adults with this disorder remains unsatisfactory. The pathophysiology of Classic Galactosemia is complex, but there is convincing evidence that galactose-1-phosphate (gal-1P) accumulation is a major, if not the sole pathogenic factor. Galactokinase (GALK) inhibition will eliminate the accumulation of gal-1P from both dietary sources and endogenous production, and efforts toward identification of therapeutic small molecule GALK inhibitors are reviewed in detail. Experimental and computational high-throughput screenings of compound libraries to identify GALK inhibitors have been conducted, and subsequent studies aimed to characterize, prioritize, as well as to optimize the identified positives have been implemented to improve the potency of promising compounds. Although none of the identified GALK inhibitors inhibits glucokinase and hexokinase, some of them cross-inhibit other related enzymes in the GHMP small molecule kinase superfamily. While this finding may render the on-going hit-to-lead process more challenging, there is growing evidence that such cross-inhibition could also lead to advances in antimicrobial and anti-cancer therapies. © 2011 Elsevier Inc. Source

Santoro S.L.,Section of Genetics | Santoro S.L.,Ohio State University | Martin L.J.,Cincinnati Childrens Hospital Medical Center | Martin L.J.,University of Cincinnati | And 3 more authors.
Journal of Pediatrics | Year: 2016

Objectives To assess adherence to the 2011 American Academy of Pediatrics (AAP) health supervision guidelines for Down syndrome, to determine whether pediatrician education improves adherence, and to evaluate stakeholder attitudes toward these guidelines. Study design Twenty-two pediatric care sites participated in chart review of adherence to the components of the AAP guidelines for Down syndrome in this longitudinal cohort study. We analyzed universal recommendations which apply to all children with Down syndrome. Thirteen pediatric practices caring for 82 patients with Down syndrome received educational information. Frequency calculations with Bonferroni adjustment of the P value threshold (P =.05/9 =.0056) were performed. Adherence rates were compared between cohorts and within the individual before and after intervention using 2 × 2 contingency tables and goodness-of-fit tests. Pediatricians and parents of children with Down syndrome completed an anonymous survey regarding their attitudes toward the guidelines. Results Statistically significant increases in adherence were seen in 5 of the 8 universal recommendations following pediatrician education (P ≤.002), including cardiology and genetics visits, rates of echocardiography, annual audiology testing, and sleep studies by age 4 years. Both physicians and parents reported generally positive views of the guidelines, yet baseline adherence rates were suboptimal. Pediatrician education preferences include directly integrating the guidelines into an electronic medical record system. Conclusion Stakeholder attitudes reflect a willingness to follow the AAP guidelines for Down syndrome. Providing rapid access to simple, clear reminders of recommended assessments successfully improved adherence to the AAP guidelines for Down syndrome. © 2016 Elsevier Inc. Source

Lale S.,Truman Medical Center | Ardinger H.,Section of Genetics | Mardis N.,Childrens Mercy Hospital and Clinics | Changho S.,Childrens Mercy Hospital and Clinics | And 2 more authors.
Pediatric and Developmental Pathology | Year: 2011

Total absence of ribs is a rare finding that has occasionally been documented in patients with cerebrocostomandibular syndrome. Only 2 other reports document complete absence of ribs in 3 individuals, and we tabulate the findings of all the 4 cases of complete absence of ribs in this case report. Our case and the other 3 reported cases represent the extreme form of cerebrocostomandibular syndrome with regard to the costal defects. © 2011 Society for Pediatric Pathology. Source

Larsen H.A.S.,Institute of Basic science and Aquatic Medicine | Austbo L.,Section of Genetics | Morkore T.,Nofima Marin AS | Thorsen J.,University of Oslo | And 5 more authors.
Fish and Shellfish Immunology | Year: 2012

Melanin comprises a complex group of pigmented polymers whose primary function is ascribed to dermal solar protection, but may also have an interesting role in innate immunity. In ectothermic vertebrates, melanogenesis is reported in leukocyte populations, but it is not known if this occurs in connection with inflammatory reactions. Melanin accumulations in ectopic locations, in particular muscle, represent a serious quality problem in salmon production. Here, we investigated such changes for the expression of dopachrome tautomerase and tyrosinase as well as some important immune genes and pathogens. Furthermore, the nature of the pathological changes was addressed by morphological methods. Gene transcripts encoding key enzymes in melanogenesis, suggesting a de novo melanin synthesis in pigmented muscle, were found. MHC class II transcripts were up-regulated and there was no indication of bacterial or viral infection. The histological examination revealed granulomatous inflammation with distribution of MHC class II positive cells and T cells, analogous to the pattern found in mammals. Importantly, in contrast to mammals pigmented cells were contributing in the inflammation. We demonstrate that melanin production occurs in granulomatous inflammation in salmon, revealing a close and hitherto unreported link between the pigmentary and immune systems. © 2012 Elsevier Ltd. Source

Discover hidden collaborations