A5073631988- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Metabolism and Genetic Disorders
- Pancreatic function and diabetes
- Diabetes Management and Research
- Diet and metabolism studies
- Metabolism, Diabetes, and Cancer
- Mitochondrial Function and Pathology
- Diabetes and associated disorders
- Neuroblastoma Research and Treatments
- Amino Acid Enzymes and Metabolism
- Cardiac Ischemia and Reperfusion
- Glycogen Storage Diseases and Myoclonus
- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Neonatal Respiratory Health Research
- Neuroendocrine Tumor Research Advances
- Peroxisome Proliferator-Activated Receptors
- Neonatal Health and Biochemistry
- Biochemical and Molecular Research
- Cardiac Arrest and Resuscitation
- Folate and B Vitamins Research
- Enzyme Structure and Function
- Mechanical Circulatory Support Devices
- Cardiovascular Function and Risk Factors
- Growth Hormone and Insulin-like Growth Factors
Children's Hospital of Philadelphia
2016-2025
University of Pennsylvania
2016-2025
Vitalant
2023
Philadelphia University
2001-2022
Adult Congenital Heart Association
2018
Guerbet (France)
2015
Pediatrics and Genetics
2010
Cook Children's Medical Center
2006
Donald Danforth Plant Science Center
2003-2004
Sunderland Royal Hospital
2004
A new form of congenital hyperinsulinism characterized by hypoglycemia and hyperammonemia was described recently. We hypothesized that this syndrome caused excessive activity glutamate dehydrogenase, which oxidizes to α-ketoglutarate is a potential regulator insulin secretion in pancreatic beta cells ureagenesis the liver.
Spontaneous hyperinsulinemic hypoglycemia in adults is most frequently caused by sporadic, solitary pancreatic beta-cell tumors, whereas childhood commonly generalized dysfunction.1 Mutations the sulfonylurea-receptor (SUR1) gene or inward-rectifying potassium-channel (Kir6.2) were found some patients.2–7 A distinct syndrome of hyperinsulinism with hyperammonemia was recently described,8,9 apparently mutations glutamate dehydrogenase gene.10 However, many sporadic and familial cases remain...
During the first 24-48 hours of life, as normal neonates transition from intrauterine to extrauterine their plasma glucose (PG) concentrations are typically lower than later in life.1Cornblath M. Reisner S.H. Blood neonate and its clinical significance.N Engl J Med. 1965; 273: 378-381Crossref PubMed Scopus (116) Google Scholar, 2Srinivasan G. Pildes R.S. Cattamanchi Voora S. Lilien L.D. Plasma values neonates: a new look.J Pediatr. 1986; 109: 114-117Abstract Full Text PDF (225) 3Stanley C.A....
Hypoglycemia due to congenital hyperinsulinism (HI) is caused by mutations in 9 genes. Our objective was correlate genotype with phenotype 417 children HI. Mutation analysis carried out for the ATP-sensitive potassium (KATP) channel genes (ABCC8 and KCNJ11), GLUD1, GCK supplemental screening of rarer genes, HADH, UCP2, HNF4A, HNF1A, SLC16A1. Mutations were identified 91% (272 298) diazoxide-unresponsive probands (ABCC8, KCNJ11, GCK), 47% (56 118) diazoxide-responsive HNF1A). In diffuse...
Congenital disorders of glycosylation are genetic syndromes that result in impaired glycoprotein production. We evaluated patients who had a novel recessive disorder glycosylation, with range clinical manifestations included hepatopathy, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, and cardiac arrest.Homozygosity mapping followed by whole-exome sequencing was used to identify mutation the gene for...
<b><i>Background:</i></b> Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and severe cause persistent hypoglycemia in infants children. In 65 years since HI children was first described, there has been a dramatic advancement diagnostic tools available, including new genetic techniques novel radiologic imaging for focal HI; however, have almost no therapeutic modalities development diazoxide....
CARNITINE (β-hydroxy-γ-trimethylaminobutyric acid) is an essential cofactor for the oxidation of fatty acids by mitochondria. It serves to carry long-chain in form their acyl-carnitine esters across barrier inner mitochondrial membrane before β-oxidation. Since 1973,1 a total 46 patients have been described with evidence impaired acid associated reduced levels carnitine.2 These divided into group "systemic carnitine deficiency," which presents infancy or early childhood recurrent episodes...
Familial hyperinsulinism (HI) is a disorder of pancreatic beta-cell function characterized by persistent despite severe hypoglycemia. To define the molecular genetic basis HI in Ashkenazi Jews, 25 probands were screened for mutations sulfonylurea receptor (SUR1) gene single-strand conformation polymorphism (SSCP) analysis genomic DNA and subsequent nucleotide sequence analyses. Two common identified: (I) novel in-frame deletion three nucleotides (nt) exon 34, resulting codon F1388 (delta...
To determine the implication of decreased T3 production during fasting, seven normal men were fasted for 80 hours on two occasions; they received 5 microgram every three durnig second fast. The mean serum concentration declined control fast from 120 to 73 ng per deciliter (P less than 0.01), but remained slightly above base-line values Mean T4 concentrations did not change, and rT3 increased, both fasts. peak TSH increment after TRH was 11.1 micromicron milliliter before 8.9 (not...
ATP-sensitive potassium (KATP) channels are an essential component of glucose-dependent insulin secretion in pancreatic islet β-cells. These comprise the sulfonylurea receptor (SUR1) and Kir6.2, a member inward rectifier K+ channel family. Mutations SUR1 subunit associated with familial hyperinsulinism (HI) (MIM:256450), inherited disorder characterized by neonate. Since Kir6.2 gene maps to human chromosome 11p15.1 (1,2), which also encompasses locus for HI, we screened presence mutations 78...
Genome-wide association studies (GWAS) have been fruitful in identifying disease susceptibility loci for common and complex diseases. A remaining question is whether we can quantify individual risk based on genotype data, order to facilitate personalized prevention treatment Previous typically failed achieve satisfactory performance, primarily due the use of only a limited number confirmed loci. Here propose that sophisticated machine-learning approaches with large ensemble markers may...
Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, one of the most common inherited metabolic disorders, is often mistaken for sudden infant death syndrome or Reye's syndrome. Diagnosing it has been difficult because a lack fast and reliable diagnostic methods. We developed stable-isotope dilution method to measure urinary n-hexanoylglycine, 3-phenylpropionylglycine, suberylglycine, we retrospectively tested its accuracy in diagnosing MCAD deficiency. measured concentrations these three...
Congenital hyperinsulinism is a condition of dysregulated insulin secretion often caused by inactivating mutations the ATP-sensitive K+ (KATP) channel in pancreatic β cell. Though most disease-causing 2 genes encoding KATP subunits, ABCC8 (SUR1) and KCNJ11 (Kir6.2), are recessively inherited, some cases dominantly inherited have been reported. To better understand differences between mutations, we identified characterized 16 families with 14 different including total 33 affected individuals....
MITOCHONDRIAL oxidation of fatty acids provides the chief source energy during prolonged fasting as well for cardiac muscle and skeletal exercise. In past decade, 10 genetic defects this pathway have been recognized in infants children.1 2 3 4 5 6 7 Although each these disorders is rare, failure to recognize them can deprive patients lifesaving therapy. Patients with present coma after a period starvation hypoketosis — that is, their serum ketone concentrations are low. They may also...
Inflammatory bowel disease, including Crohn's disease (CD) and ulcerative colitis (UC), type 1 diabetes (T1D) are autoimmune diseases that may share common susceptibility pathways. We examined known loci for these in a cohort of 1689 CD cases, 777 UC 989 T1D cases 6197 shared control subjects European ancestry, who were genotyped by the Illumina HumanHap550 SNP arrays. identified multiple previously unreported or unconfirmed associations, (ICOSLG TNFSF15) (TNFAIP3) confer risk, (HERC2 IL26)...