{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:16:49Z","timestamp":1789179409544,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T00:00:00Z","timestamp":1439164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"NKH Crusaders Fund"},{"name":"Hope for NKH Fund"},{"name":"CU Nonketotic Hyperglycinemia Fund"},{"name":"Joseph's Goal Fund"},{"name":"Brodyn's Friends Fund"},{"name":"Smiles for Miles NKH Research Fund"},{"name":"Lucy's BEElievers Fund"},{"name":"Madi's Mission to Find a Cure for NKH Fund"},{"name":"Les Petits Bourdons"},{"name":"Children's Clinical Research Organization at Children's Hospital Colorado"},{"name":"Rocky Mountain Neurological Disorders Core Center","award":["NIH\/NS048154"],"award-info":[{"award-number":["NIH\/NS048154"]}]},{"name":"University of Colorado DNA Sequencing and Analysis Core"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Nonketotic hyperglycinemia is a neurometabolic disorder characterized by intellectual disability, seizures, and spasticity. Patients with attenuated nonketotic hyperglycinemia make variable developmental progress. Predictive factors have not been systematically assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reviewed 124 patients stratified by developmental outcome for biochemical and molecular predictive factors. Missense mutations were expressed to quantify residual activity using a new assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with severe nonketotic hyperglycinemia required multiple anticonvulsants, whereas patients with developmental quotient (DQ)\u2009&gt;\u200930 did not require anticonvulsants. Brain malformations occurred mainly in patients with severe nonketotic hyperglycinemia (71%) but rarely in patients with attenuated nonketotic hyperglycinemia (7.5%). Neonatal presentation did not correlate with outcome, but age at onset\u2009\u2265\u20094 months was associated with attenuated nonketotic hyperglycinemia. Cerebrospinal fluid (CSF) glycine levels and CSF:plasma glycine ratio correlated inversely with DQ; CSF glycine\u2009&gt;\u2009230 \u03bcM indicated severe outcome and CSF:plasma glycine ratio\u2009\u2264\u20090.08 predicted attenuated outcome. The glycine index correlated strongly with outcome. Molecular analysis identified 99% of mutant alleles, including 96 novel mutations. Mutations near the active cleft of the P\u2010protein maintained stable protein levels. Presence of 1 mutation with residual activity was necessary but not sufficient for attenuated outcome; 2 such mutations conferred best outcome. Divergent outcomes for the same genotype indicate a contribution of other genetic or nongenetic factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Accurate prediction of outcome is possible in most patients. A combination of 4 factors available neonatally predicted 78% of severe and 49% of attenuated patients, and a score based on mutation severity predicted outcome with 70% sensitivity and 97% specificity. Ann Neurol 2015;78:606\u2013618<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24485","type":"journal-article","created":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T11:22:28Z","timestamp":1436959348000},"page":"606-618","source":"Crossref","is-referenced-by-count":97,"title":["Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia"],"prefix":"10.1002","volume":"78","author":[{"given":"Michael A.","family":"Swanson","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Curtis R.","family":"Coughlin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter H.","family":"Scharer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather J.","family":"Szerlong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra J.","family":"Bjoraker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine B.","family":"Spector","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geralyn","family":"Creadon\u2010Swindell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Mahieu","sequence":"additional","affiliation":[{"name":"Center for Human Genetics University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Matthijs","sequence":"additional","affiliation":[{"name":"Center for Human Genetics University of Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia B.","family":"Hennermann","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine University Medical Center Mainz Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek A.","family":"Applegarth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Toone","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhong","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado Aurora CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan L. 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