Braunlin E.,University of Minnesota |
Wang R.,CHOC Childrens |
Wang R.,University of California at Irvine
Heart | Year: 2016
The growing availability of innovative treatments for rare genetic diseases with a cardiac component-such as the mucopolysaccharidoses (MPSs)-has changed these syndromes from 'back of the textbook' curiosities of childhood to chronic, but rare, adult cardiac conditions that require both centres of expertise and knowledgeable subspecialists. The MPSs are inherited progressive lysosomal storage diseases, occurring in about 1:25 000 births and resulting from absence of functional hydrolases responsible for the degradation of glycosaminoglycans, naturally occurring complex sugars ubiquitous throughout the body. In the heart, accumulation of glycosaminoglycans occurs within the cardiac valves, the epicardial coronary arteries, the myocytes and cardiac interstitium and the walls of the great vessels. As a consequence, cardiac valve regurgitation and stenosis, diffuse coronary artery stenosis, myocardial dysfunction and aortic root dilation often occur. Haematopoietic cell transplantation and enzyme replacement therapy have changed the previously lethal natural history of the MPSs to one of survival well into adulthood. Despite this improved lifespan, the left-sided cardiac valves continue to show progressive functional involvement and cardiac valve replacement is not uncommon, especially in adults. The risk of any intervention is increased in these patients because of the systemic effects of the disease on the respiratory system and cervical cord. Our current understanding of other cardiac issues in adults with the MPSs, especially with the coronary circulation and myocardium, is meagre and more needs to be known to effectively care for this emerging population of adults. Incorporation of the MPSs, as well as other nowtreatable rare diseases, into the educational curriculum of current and future adult subspecialists is an important next step.
News Article | July 18, 2017
The new unit, located on the fourth floor of CHOC's Bill Holmes Tower, creates a homey atmosphere with sleeping quarters and storage space outfitted in warm colors and wooden accents to help parents feel more comfortable while their infants receive highly specialized care for extended periods of time. "CHOC is proud to offer private rooms to our smallest patients and their parents," said Dr. Vijay Dhar, medical director of CHOC's NICU. "No one's vision of parenthood includes a NICU stay, but our new unit will provide parents with the space and privacy to get to know their new baby, and reassurance that they'll be nearby while their newborn receives the highest level of care." Private NICU rooms are a new standard for improved patient outcomes. Benefits for babies cared for in single-family rooms include higher weight at discharge and more rapid weight gain. Also, they require fewer medical procedures and experience less stress, lethargy and pain. Researchers have attributed these findings to increased maternal involvement. A private-room setting provides space and privacy sought by parents to breastfeed, practice skin-to-skin bonding, and be more intimately involved in their baby's care. Further, individual rooms allow parents to stay overnight with their newborn, and give staff more access and interaction with the family and patient. In addition to private rooms, the new space includes other features that will enhance patient care. Should an infant need a sudden surgical procedure, three rooms within the unit can quickly be converted into space for surgeries. The unit will also include a life-saving extracorporeal membrane oxygenation (ECMO) unit. Rooms that adjoin can be used to accommodate triplets. Safety features include same-handed rooms, wherein equipment is positioned in the same location among all rooms to reduce human error; room-adjacent nursing alcoves; and an in-unit nutrition lab for the preparation of breast milk and formula. CHOC's new unit also features a family dining space, a room dedicated for siblings, a lactation room and other amenities to ensure the comfort of the entire family. For several decades, CHOC has served infants requiring the highest level of care. With the unit's opening, CHOC's neonatal services now include 72 beds at CHOC Orange and the CHOC Children's NICU at St. Joseph Hospital, and 22 beds at CHOC Children's at Mission Hospital. In addition, a team of premier CHOC neonatologists care for babies at hospitals throughout Southern California. A suite of specialized services comprises the CHOC NICU: the Surgical NICU, which provides dedicated care to babies needing or recovering from surgery; the Small Baby Unit, where infants with extremely low birth weights receive coordinated care; the Neurocritical NICU, where babies with neurological problems are cohorted; and the Cardiac NICU, which provides comprehensive care for neonates with congenital heart defects. Visit www.choc.org/nicu to learn more about CHOC's neonatal services. Named one of the best children's hospitals by U.S. News & World Report (2017-2018) and a 2016 Leapfrog Top Hospital for the highest quality of care, Children's Hospital of Orange County (CHOC Children's) is exclusively committed to the health and well-being of children through clinical expertise, advocacy, outreach, education and research that brings advanced treatment to pediatric patients. Affiliated with the University of California, Irvine, CHOC's regional health care network includes two state-of-the-art hospitals in Orange and Mission Viejo, many primary and specialty care clinics, a pediatric residency program, and four clinical centers of excellence - the CHOC Children's Heart, Neuroscience, Orthopaedic and Hyundai Cancer Institutes. CHOC earned the Gold Level CAPE Award from the California Council of Excellence, the only children's hospital in California to ever earn this distinction, and was awarded Magnet designation, the highest honor bestowed to hospitals for nursing excellence. Recognized for extraordinary commitment to high-quality critical care standards, CHOC's Pediatric Intensive Care Unit (PICU) is the first in the United States to earn the Beacon Award for Pediatric Critical Care Excellence.
Puckett R.L.,CHOC Childrens |
Rinaldo P.,Rochester College |
Lipson M.H.,Kaiser Permanente |
Matern D.,Rochester College |
And 4 more authors.
Molecular Genetics and Metabolism | Year: 2010
Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has allowed for early detection and initiation of treatment in many patients with maple syrup urine disease (MSUD) (OMIM 248600), however, a recent report suggests that variants forms may be missed. Information on these patients is limited. We present clinical, biochemical and molecular information on patients with variant forms of MSUD not detected by the California Newborn Screening Program. Between July 2005 and July 2009, 2200,000 newborns were screened in California by MS/MS. Seventeen cases of MSUD were detected and three (two siblings) were missed. Additionally, the NBS cards of two siblings with late onset MSUD, who were born pre-expanded NBS, were retrospectively analyzed. None of the five patients met criteria to be considered presumptive positive for MSUD (leucine > 200 μmol/L and a ratio of leucine/alanine ≥ 1.5). Alloisoleucine (allo-ile) was subsequently analyzed in the NBS cards of all five patients, two of whom were found to have elevated levels. The proband in each family was diagnosed following symptoms triggered by an intercurrent illness or increased protein intake. At diagnosis, leucine levels ranged between 561 and >4528 μmol/L, and allo-ile ranged from 137 to 239 μmol/L. Two affected siblings had normal plasma amino acids when asymptomatic; however, their biochemical profiles were diagnostic of MSUD during intercurrent illnesses. The median age at diagnosis of all patients was one year (range 0.8-6.7). Heterozygous BCKDHB (E1β) mutations (c.832G > A/c.970C > T) were identified in one family and a homozygous DBT (E2) sequence variant (c.1430 T > G) in another. The third family had one identifiable DBT mutation (c.827T > G), however, a second mutation was not detected. This report provides further evidence that NBS by MS/MS is unable to detect all cases of MSUD. Second-tier testing with allo-ile may improve sensitivity; however, some children with variant forms will invariably be missed. © 2009 Elsevier Inc.
Wang R.Y.,CHOC Childrens |
Bodamer O.A.,University of Miami |
Watson M.S.,Medical College of Wisconsin |
Wilcox W.R.,Cedars Sinai Medical Center |
Wilcox W.R.,University of California at Los Angeles
Genetics in Medicine | Year: 2011
PURPOSE: To develop educational guidelines for the diagnostic confirmation and management of individuals identified by newborn screening, family-based testing after proband identification, or carrier testing in at-risk populations, and subsequent prenatal or postnatal testing of those who are presymptomatic for a lysosomal storage disease. METHODS: Review of English language literature and discussions in a consensus development panel comprised an international group of experts in the clinical and laboratory diagnosis, treatment and management, newborn screening, and genetic aspects of lysosomal storage diseases. RESULTS: Although clinical trial and longitudinal data were used when available, the evidence in the literature is limited and consequently the recommendations must be considered as expert opinion. Guidelines were developed for Fabry, Gaucher, and Niemann-Pick A/B diseases, glycogen storage type II (Pompe disease), globoid cell leukodystrophy (Krabbe disease), metachromatic leukodystrophy, and mucopolysaccharidoses types I, II, and VI. CONCLUSION: These guidelines serve as an educational resource for confirmatory testing and subsequent clinical management of presymptomatic indivduals suspected to have a lysosomal storage disease; they also help to define a research agenda for longitudinal studies such as the American College of Medical Genetics/National Institutes of Health Newborn Screening Translational Research Network. © 2011 Lippincott Williams & Wilkins.
He M.,University of Pennsylvania |
Smith L.D.,Childrens Mercy Hospital |
Chang R.,CHOC Childrens |
Li X.,University of Pennsylvania |
Vockley J.,University of Pittsburgh
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2014
Deficiency of sterol C4 methyl oxidase, encoded by the SC4MOL gene, has recently been described in four patients from three different families. All of the patients presented with microcephaly, congenital cataracts, and growth delay in infancy. The first patient has suffered since the age of six years from severe, diffuse, psoriasiform dermatitis, sparing only her palms. She is now 20 years old. The second patient is a 5 year old girl who has just started to develop dry skin and hair changes. The third and fourth patients are a pair of affected siblings with a severe skin condition since infancy. Quantitative sterol analysis of plasma and skin scales from all four patients showed marked elevation of 4α-methyl- and 4, 4′-dimethylsterols, consistent with a deficiency in the first step of sterol C4 demethylation in cholesterol biosynthesis. Mutations in the SC4MOL have been identified in all of the patients. SC4MOL deficiency is the first autosomal recessive disorder identified in the sterol demethylation complex. Cellular studies with patient-derived fibroblasts have shown a higher mitotic rate than control cells in cholesterol-depleted medium, with increased de novo cholesterol biosynthesis and accumulation of methylsterols. Immunologic analyses of granulocytes and B cells from patients and obligate carriers in the patients' families indicated dysregulation of immune-related receptors. Inhibition of sterol C4 methyl oxidase in human transformed lymphoblasts induced activation of the cell cycle. Additional studies also demonstrated diminished EGFR signaling and disrupted vesicular trafficking in cells from the affected patients. These findings suggest that methylsterols play an important role in epidermal biology by their influence on cell proliferation, intracellular signaling, vesicular trafficking and immune response. SC4MOL is situated within the psoriasis susceptibility locus PSORS9, and may be a genetic risk factor for common skin conditions. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. © 2013 Elsevier B.V.
PubMed | University of California at Irvine, Illinois College, CHOC Childrens, University of California at Los Angeles and 3 more.
Type: Comparative Study | Journal: Journal of electrocardiology | Year: 2015
The spatial peaks QRS-T angle has been shown to differentiate adult patients with hypertrophic cardiomyopathy (HCM) from controls. We hypothesized that the spatial peaks QRS-T angle would, in isolation, be more accurate than the Italian 12-lead ECG Pre-participation Screening criteria or the Seattle criteria for detecting hypertrophic cardiomyopathy (HCM) in pediatric patients.A retrospective study of pediatric patients with HCM compared to age and gender-matched control patients was undertaken. Significance, odds ratios, sensitivity and specificity of HCM detection of the visually derived spatial peaks QRS-T angle were compared to those of traditional 12-lead ECG criteria using: 1) Italys National Pre-participation Screening Programme criteria; and 2) described criteria from Seattle.ECG results from 130 pediatric HCM patients (14.24.4years) were compared to 470 control patients (normal echocardiograms, mean age 13.44.6years). Meanstandard deviation (SD) values for spatial peaks QRS-T angles were 120.440.7 and 21.313.7 degrees for HCM and controls, respectively (P<0.001). A spatial peaks QRS-T angle cutoff value of >54.9 degrees yielded greater sensitivity and specificity (93.1% and 98.7%, respectively) for detecting HCM over ECG criteria from Italy (68.5% and 48.1%, respectively) or Seattle (64.6% and 78.9%, respectively) with odds ratios at 1039.70 (95% CI 363.03 to 2977.67), 2.01 (95% CI 1.33 to 3.04) and 6.84 (4.49-10.44), respectively.In our cohort, a visually derived spatial peaks QRS-T angle has increased sensitivity and specificity for detection of HCM in pediatric patients compared to currently utilized Italian or Seattle ECG criteria.
Miyake N.,Yokohama City University |
Yano S.,University of Southern California |
Sakai C.,National Institute of Neuroscience |
Hatakeyama H.,National Institute of Neuroscience |
And 14 more authors.
Human Mutation | Year: 2013
Mitochondrial complex III (CIII) deficiency is a relatively rare disease with high clinical and genetic heterogeneity. CIII comprises 11 subunits encoded by one mitochondrial and 10 nuclear genes. Abnormalities of the nuclear genes such as BCS1L and TTC19 encoding mitochondrial assembly factors are well known, but an explanation of the majority of CIII deficiency remains elusive. Here, we report three patients from a consanguineous Mexican family presenting with neonatal onset of hypoglycemia, lactic acidosis, ketosis, and hyperammonemia. We found a homozygous missense mutation in UQCRC2 that encodes mitochondrial ubiquinol-cytochrome c reductase core protein II by whole-exome sequencing combined with linkage analysis. On the basis of structural modeling, the mutation (p.Arg183Trp) was predicted to destabilize the hydrophobic core at the subunit interface of the core protein II homodimer. In vitro studies using fibroblasts from the index patient clearly indicated CIII deficiency, as well as impaired assembly of the supercomplex formed from complexes I, III, and IV. This is the first described human disease caused by a core protein abnormality in mitochondrial CIII. © 2012 Wiley Periodicals, Inc.
PubMed | University of California at Irvine and CHOC Childrens
Type: | Journal: Molecular genetics and metabolism reports | Year: 2016
Biotin-thiamine responsive basal ganglia disease (BTBGD) is a rare metabolic condition caused by mutations in the
Sowa M.,CHOC Children's |
Steele C.,CHOC Children's
Infant, Child, and Adolescent Nutrition | Year: 2015
The (CNL) Clinical Nutrition and Lactation Department developed a pediatric registered dietitian (RD) residency program designed to provide training for new dietitians or those looking to transition to the area of pediatric nutrition. External funding to support the program was received through private donors. Residency rotations included a variety of specialty areas in both the inpatient and outpatient settings. Curriculum for each specialty area included text and journal references, a slide presentation providing an overview of the area, and a pretest to assess baseline knowledge. During each rotation, the RD resident worked alongside the preceptor and was given opportunities to provide medical nutrition therapy with increasing autonomy. Each specialty rotation ended with a post-test or case study and monthly evaluations were used to review feedback from each preceptor. A pediatric RD residency program is beneficial to both the hospital and the dietetics profession. The organization can train and evaluate an individual for 16 weeks in the clinical setting before potentially hiring. Such a program also fills the need for pediatric training, beyond the clinical internship, for those pursuing a career in pediatric nutrition. © 2014 The Author(s).
Williams T.B.,CHOC Childrens |
Daniels M.,CHOC Childrens |
Puthenveetil G.,CHOC Childrens |
Chang R.,CHOC Childrens |
And 2 more authors.
Molecular Genetics and Metabolism | Year: 2012
Purpose: Pearson syndrome is a very rare metabolic disorder that is usually present in infancy with transfusion dependent macrocytic anemia and multiorgan involvement including exocrine pancreas, liver and renal tubular defects. The disease is secondary to a mitochondrial DNA deletion that is variable in size and location. Endocrine abnormalities can develop, but are usually not part of the initial presentation. We report two patients who presented with unusual endocrine manifestations, neonatal diabetes and adrenal insufficiency, who were both later diagnosed with Pearson syndrome. Methods: Medical records were reviewed. Confirmatory testing included: mitochondrial DNA deletion testing and sequencing of the breakpoints, muscle biopsy, and bone marrow studies. Results: Case 1 presented with hyperglycemia requiring insulin at birth. She had several episodes of ketoacidosis triggered by stress and labile blood glucose control. Workup for genetic causes of neonatal diabetes was negative. She had transfusion dependent anemia and died at 24. months due to multisystem organ failure. Case 2 presented with adrenal insufficiency and anemia during inturcurrent illness, requiring steroid replacement since 37. months of age. He is currently 4. years old and has mild anemia. Mitochondrial DNA studies confirmed a 4.9. kb deletion in patient 1 and a 5.1. kb deletion in patient 2. Conclusion: The patients reported highlight the importance of considering mitochondrial DNA disorders in patients with early onset endocrine dysfunction, and expand the knowledge about this rare mitochondrial disease. © 2012 Elsevier Inc.