Publications by authors named "Amanda L Bergner"

14 Publications

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Genetic Counseling for Neurofibromatosis 1, Neurofibromatosis 2, and Schwannomatosis-Practice Resource of the National Society of Genetic Counselors.

J Genet Couns 2020 10 29;29(5):692-714. Epub 2020 Jun 29.

Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.

The goal of this practice resource is to provide genetic counselors and other healthcare professionals with a resource to reference when providing genetic counseling services to individuals and families undergoing evaluation for neurofibromatosis (NF) or who have received a diagnosis of NF, including NF1, NF2, and schwannomatosis. This resource represents the opinions of a multi-center working group of Certified Genetic Counselors with experience in the care of individuals with NF, providing topics to be considered for the incorporation into a clinical genetic counseling session.
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http://dx.doi.org/10.1002/jgc4.1303DOI Listing
October 2020

Reflections on diversity, equity, and inclusion in genetic counseling education.

J Genet Couns 2020 04 13;29(2):315-323. Epub 2020 Mar 13.

Joan H. Marks Graduate Program in Human Genetics, Sarah Lawrence College, Bronxville, NY, USA.

Through self-reflection, self-education, and with a learning mindset each of us has embarked on a personal path to understand the impact of racism in our personal and professional lives. This personal work is ongoing, though it was through our individual paths that led us to engage in dialogue on race and racism at the 38th National Society of Genetic Counselors Annual Conference. We initially did not know each other; however, we were drawn by a mutual desire to further the conversation and sought connection with each other after the Conversations Around Diversity Platform Presentations. Through sustained, open dialogue we created a brave space for sharing our emotional and intellectual responses to the conference. Through this dialogue and through written reflections, we recognized an emboldened urgency to author a joint reflection on our shared responsibility as genetic counseling training program leaders to use our privilege in service to our students and future students. We have the evidence that we are not a diverse profession. We have more evidence now than we did before that our profession performs poorly with regards to inclusivity. Our inability to acknowledge, address, and discuss racism and other forms of oppression is damaging to each of us individually and as a group of professionals. We owe it to ourselves, our students, our patients, and colleagues to name our learned biases and behaviors, own them and interrupt them.
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http://dx.doi.org/10.1002/jgc4.1242DOI Listing
April 2020

Improvement in Patient-reported Hearing After Treatment With Bevacizumab in People With Neurofibromatosis Type 2.

Otol Neurotol 2018 06;39(5):632-638

Department of Neurology and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts.

Objective: Assess patient-reported outcomes (PRO) for hearing and tinnitus relative to clinical hearing assessment in people with neurofibromatosis 2 (NF2) associated hearing loss.

Study Design: Prospective, open label, phase-II clinical trial with PRO administered pre-, post-, and after treatment.

Setting: Three tertiary referral centers.

Patients: Fourteen patients with NF2, median age of 30 years (range, 14-79 yr) and progressive hearing loss (median baseline word recognition score, 60%; range, 13-82%). Half of these patients achieved objective hearing response (word recognition score improved beyond the 95% critical difference versus baseline).

Intervention: Bevacizumab 7.5 mg/kg was administered every 3 weeks for 48 weeks, followed by surveillance for 24 weeks off-drug.

Main Outcome Measures: Speech, spatial, and qualities of hearing scale (SSQ) and tinnitus reaction questionnaire (TRQ) to assess hearing difficulties in life situations and tinnitus related distress.

Results: Patient-reported speech understanding and auditory quality improved with bevacizumab treatment and were significantly correlated with word recognition scores, but not pure tone threshold average. There was no change in spatial perception after treatment. Reduction in tinnitus distress after treatment with bevacizumab did not reach statistical significance.

Conclusion: Participants had reductions in hearing difficulty during treatment with bevacizumab, suggesting that patients subjectively experience hearing-related benefit mirroring clinical hearing assessments. We suspect the lack of significant reduction in tinnitus distress is related to small sample size and low intensity of distress in our sample. These data highlight the usefulness of PRO measures to assess benefits of treatment in the setting of NF2-associated hearing loss.
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http://dx.doi.org/10.1097/MAO.0000000000001781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642810PMC
June 2018

Enrolling Genomics Research Participants through a Clinical Setting: the Impact of Existing Clinical Relationships on Informed Consent and Expectations for Return of Research Results.

J Genet Couns 2018 02 20;27(1):263-273. Epub 2017 Sep 20.

McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, 600 North Wolfe Street, Blalock 1008, Baltimore, MD, 21287, USA.

Genetic counselors working in a clinical setting may find themselves recruiting, enrolling, and returning results for genomic research, and existing clinical relationships with study participants may impact these research interactions. We present a qualitative study using semi-structured interviews of participants enrolled in a genome sequencing/exome sequencing (GS/ES) study at the same institution where they receive clinical care. Interviews were coded for motivations to participate and expectations of this research. The interviews revealed common motivations for participation, including altruism and hope for benefit for themselves, family members, and/or others with their condition. Additionally, themes emerged related to unintentional influence based on trust of the clinical provider that recruited them to the study. Participant trust in the enrolling provider at times appeared to extend to the study team to decide which research results to return and to do so in an appropriate format. Participants also based expectations for research results return on previous clinical genetic testing experiences, which may or may not be realistic depending on study design. It is imperative that genetic counselors enrolling patients into research studies be aware of the potential influence of their clinical relationship on potential subjects, be transparent about their role on the study team, and help set expectations about the study process, including results return.
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http://dx.doi.org/10.1007/s10897-017-0143-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539290PMC
February 2018

Choices for return of primary and secondary genomic research results of 790 members of families with Mendelian disease.

Eur J Hum Genet 2017 05 8;25(5):530-537. Epub 2017 Mar 8.

Department of Medicine, Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA.

Although consensus is building that primary (PR) and secondary findings (SF) from genomic research should be offered to participants under some circumstances, data describing (1) actual choices of study participants and (2) factors associated with these choices are limited, hampering study planning. We conducted a cross-sectional analysis of choices made for return of PR and SF during informed consent by members of the first 247 families (790 individuals) enrolled in the Baylor-Hopkins Center for Mendelian Genomics, a genome sequencing study. Most (619; 78.3%) chose to receive SF and PR, 66 (8.4%) chose PR only, 65 (8.2%) wanted no results, and 40 (5.1%) chose SF only. Choosing SF was associated with an established clinical diagnosis in the proband (87.8 vs 79%, P=0.009) and European ancestry (EA) (87.7 vs 73%, P<0.008). Participants of non-European ancestry (NEA) were as likely as those of EA to choose SF when consented by a genetic counselor (GC) (82% NEA vs 88.3% EA, P=0.09) but significantly less likely when consented by a physician (67.4% NEA vs 85.4% EA, P=0.001). Controlling for proband diagnosis, individuals of NEA were 2.13-fold (95% CI: 1.11-4.08) more likely to choose SF when consented by a GC rather than a physician. Participants of NEA were 3-fold more likely than those of EA to decline all study results (14.7% NEA vs 5.4% EA, P<0.008). In this ethnically diverse population, whereas most participants desired PR and SF, more than 20% declined some or all results, highlighting the importance of research participant choice.
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http://dx.doi.org/10.1038/ejhg.2017.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437901PMC
May 2017

The Dynamics of a Genetic Counseling Peer Supervision Group.

J Genet Couns 2017 Jun 13;26(3):532-540. Epub 2016 Sep 13.

American College of Medical Genetics and Genomics, Bethesda, MD, USA.

Supervision is a practice that is utilized by a variety of practitioners to hone their counseling skills. Genetic counselors have embraced the supervision process, and some seek out supervision in a group setting with peers. Researchers have described the structure and content of genetic counseling peer supervision groups, and provided evidence for the benefits of seeking peer supervision. This study aimed to describe the interpersonal aspects of one genetic counseling peer supervision group, including personality traits and group dynamics, and how those factors influenced our experiences within the group. We also describe how the process of evaluating these factors impacted us individually and collectively. There was consensus that the group was a safe and trusting one, which was united by similar goals and mutual respect. Members reported gaining insights about how their own personality functioned within the group milieu, and also how the group setting impacted them. Based on our experiences, we recommend that other peer supervision groups consider similar self-evaluations on a periodic basis, both to enhance group functioning and to allow for increased self-awareness and professional growth.
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http://dx.doi.org/10.1007/s10897-016-0013-3DOI Listing
June 2017

Patient-reported outcomes of pain and physical functioning in neurofibromatosis clinical trials.

Neurology 2016 Aug;87(7 Suppl 1):S4-S12

From the Pediatric Oncology Branch (P.L.W., S.M., A.B.), National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Neurology and Cancer Center (V.L.M.), Massachusetts General Hospital, Boston; University of Chicago Pritzker School of Medicine (J.H.T.), IL; Department of Psychological Sciences (S.E.S.), University of Vermont, Burlington; Departments of Neurology and Genetics (A.L.B.), Johns Hopkins University, Baltimore, MD; Children's National Health System & The George Washington School of Medicine (K.W.), Washington, DC; Department of Speech Pathology & Audiology (H.L.T.), California State University, Sacramento; Veteran's Administration Pittsburgh Healthcare System and University of Pittsburgh (K.L.G.), PA; Department of Clinical Neurosciences (C.M.H.), Spectrum Health Medical Group and College of Human Medicine, Michigan State University, East Lansing; Division of Human Genetics (E.S.), Cincinnati Children's Hospital, OH; Department of Public Health Education (W.N.D.), School of Health and Human Sciences, University of North Carolina at Greensboro; and Advocure NF2 Inc. (B.F.), Los Angeles, CA.

Objective: Tumors and other disease complications of neurofibromatosis (NF) can cause pain and negatively affect physical functioning. To document the clinical benefit of treatment in NF trials targeting these manifestations, patient-reported outcomes (PROs) assessing pain and physical functioning should be included as study endpoints. Currently, there is no consensus on the selection and use of such measures in the NF population. This article presents the recommendations of the PRO group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration for assessing the domains of pain and physical functioning for NF clinical trials.

Methods: The REiNS PRO group reviewed and rated existing PRO measures assessing pain intensity, pain interference, and physical functioning using their systematic method. Final recommendations are based primarily on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility for clinical trials.

Results: The REiNS PRO group chose the Numeric Rating Scale-11 (≥8 years) to assess pain intensity, the Pain Interference Index (6-24 years) and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Scale (≥18 years) to evaluate pain interference, and the PROMIS Physical Functioning Scale to measure upper extremity function and mobility (≥5 years) for NF clinical trials.

Conclusions: The REiNS Collaboration currently recommends these PRO measures to assess the domains of pain and physical functioning for NF clinical trials; however, further research is needed to evaluate their use in individuals with NF. A final consensus recommendation for the pain interference measure will be disseminated in a future publication based on findings from additional published research.
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http://dx.doi.org/10.1212/WNL.0000000000002927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578357PMC
August 2016

2013 Review and Update of the Genetic Counseling Practice Based Competencies by a Task Force of the Accreditation Council for Genetic Counseling.

J Genet Couns 2016 10 23;25(5):868-79. Epub 2016 Jun 23.

Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.

The first practice based competencies (PBCs) for the field of genetic counseling were adopted by the American Board of Genetic Counseling (ABGC), 1996. Since that time, there has been significant growth in established and new work settings (clinical and non-clinical) and changes in service delivery models and the roles of genetic counselors. These changes prompted the ABGC to appoint a PBC Task Force in 2011 to review the PBCs with respect to their current relevance and to revise and update them as necessary. There are four domains in the revised PBCs: (I) Genetics Expertise and Analysis (II) Interpersonal, Psychosocial and Counseling Skills (III) Education and (IV) Professional Development and Practice. There are 22 competencies, each clarified with learning objectives or samples of activities and skills; a glossary is included. New competencies were added that address genomics, genetic testing and genetic counselors' roles in risk assessment, education, supervision, conducting research and presenting research options to patients. With PBCs serving as the pre-defined abilities or outcomes of training, graduating genetic counselors will be well prepared to enter the field with a minimum level of skills and abilities. A description of the Task Force's work, key changes and the 2013 PBCs are presented herein.
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http://dx.doi.org/10.1007/s10897-016-9984-3DOI Listing
October 2016

Health-related Quality of Life of Individuals With Neurofibromatosis Type 2: Results From the NF2 Natural History Study.

Otol Neurotol 2016 06;37(5):574-9

*Department of Neurology and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts †Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland ‡Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts §Biostatistics Center, Massachusetts General Hospital, Boston, Massachusetts ||Department of Neurotology, House Clinic, Los Angeles, California.

Objective: To explore health-related quality of life (HRQoL) reported by individuals with neurofibromatosis type 2 (NF2) and to assess for correlations between HRQoL and objective measures of disease manifestations.

Study Design: Prospective observational study.

Setting: Seven international NF2 centers.

Subjects: Eighty-one individuals with NF2, 73 adults (>18 years) and 8 children/adolescents (10-17 years).

Outcome Measures: Quality of life was measured by Short Form-36 (SF-36) norm-based scores. Objective clinical measures were hearing (categorized by word-recognition scores), facial function (categorized by the House-Brackmann scale) and the volume of subjects' larger vestibular schwannoma (VS).

Results: At baseline, adults showed significant deficits in all but two subscales of the SF-36 compared with age- and gender-adjusted United States population norms. In linear regression models including age, gender, inheritance status, hearing, facial weakness and VS volume, demographic and functional measures showed no relationship to any SF-36 subscale. Larger baseline VS volume was significantly related to reduced physical role performance, reduced mental health, and increased pain (p < 0.05). In bivariate analysis, previous VS surgery was not significantly associated with baseline HRQoL; receipt of VS surgery or tumor growth during the observation period was not significantly associated with changes in HRQoL.

Conclusion: NF2 patients report reduced HRQoL in physical, social, and mental domains, but this was not significantly related to objective measures of hearing or facial functioning. Larger baseline VS volume negatively impacted patient-reported HRQoL whereas VS surgery or tumor growth did not. Future studies should explore the relationship between tumor volume and HRQoL and psychosocial factors that may moderate this relationship.
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http://dx.doi.org/10.1097/MAO.0000000000001019DOI Listing
June 2016

Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2-Associated Vestibular Schwannomas.

J Clin Oncol 2016 05 14;34(14):1669-75. Epub 2016 Mar 14.

Jaishri O. Blakeley, Xiaobu Ye, Amanda L. Bergner, Laura M. Fayad, Shivani Ahlawat, and Michael A. Jacobs, Johns Hopkins University, Baltimore; Christopher Zalewski, National Institute on Deafness and Other Communication Disorders; Eva Dombi and Brigitte C. Widemann, National Cancer Institute, Bethesda, MD; Dan G. Duda, Alona Muzikansky, Vanessa L. Merker, Elizabeth R. Gerstner, Rakesh K. Jain, and Scott R. Plotkin, Massachusetts General Hospital; and Chris F. Halpin, Massachusetts Eye and Ear Infirmary, Boston, MA.

Purpose: Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy and biomarkers of bevacizumab activity for NF2-associated progressive and symptomatic VSs.

Patients And Methods: Bevacizumab 7.5 mg/kg was administered every 3 weeks for 46 weeks, followed by 24 weeks of surveillance after treatment with the drug. The primary end point was hearing response defined by word recognition score (WRS). Secondary end points included toxicity, tolerability, imaging response using volumetric magnetic resonance imaging analysis, durability of response, and imaging and blood biomarkers.

Results: Fourteen patients (estimated to yield > 90% power to detect an alternative response rate of 50% at alpha level of 0.05) with NF2, with a median age of 30 years (range, 14 to 79 years) and progressive hearing loss in the target ear (median baseline WRS, 60%; range 13% to 82%), were enrolled. The primary end point, confirmed hearing response (improvement maintained ≥ 3 months), occurred in five (36%) of 14 patients (95% CI, 13% to 65%; P < .001). Eight (57%) of 14 patients had transient hearing improvement above the 95% CI for WRS. No patients experienced hearing decline. Radiographic response was seen in six (43%) of 14 target VSs. Three grade 3 adverse events, hypertension (n = 2) and immune-mediated thrombocytopenic purpura (n = 1), were possibly related to bevacizumab. Bevacizumab treatment was associated with decreased free vascular endothelial growth factor (not bound to bevacizumab) and increased placental growth factor in plasma. Hearing responses were inversely associated with baseline plasma hepatocyte growth factor (P = .019). Imaging responses were associated with high baseline tumor vessel permeability and elevated blood levels of vascular endothelial growth factor D and stromal cell-derived factor 1α (P = .037 and .025, respectively).

Conclusion: Bevacizumab treatment resulted in durable hearing response in 36% of patients with NF2 and confirmed progressive VS-associated hearing loss. Imaging and plasma biomarkers showed promising associations with response that should be validated in larger studies.
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http://dx.doi.org/10.1200/JCO.2015.64.3817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872317PMC
May 2016

Dystrophic spinal deformities in a neurofibromatosis type 1 murine model.

PLoS One 2015 18;10(3):e0119093. Epub 2015 Mar 18.

Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

Despite the high prevalence and significant morbidity of spinal anomalies in neurofibromatosis type 1 (NF1), the pathogenesis of these defects remains largely unknown. Here, we present two murine models: Nf1flox/-;PeriCre and Nf1flox/-;Col.2.3Cre mice, which recapitulate spinal deformities seen in the human disease. Dynamic histomorphometry and microtomographic studies show recalcitrant bone remodeling and distorted bone microarchitecture within the vertebral spine of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice, with analogous histological features present in a human patient with dystrophic scoliosis. Intriguingly, 36-60% of Nf1flox/-;PeriCre and Nf1flox/-;Col2.3Cre mice exhibit segmental vertebral fusion anomalies with boney obliteration of the intervertebral disc (IVD). While analogous findings have not yet been reported in the NF1 patient population, we herein present two case reports of IVD defects and interarticular vertebral fusion in patients with NF1. Collectively, these data provide novel insights regarding the pathophysiology of dystrophic spinal anomalies in NF1, and provide impetus for future radiographic analyses of larger patient cohorts to determine whether IVD and vertebral fusion defects may have been previously overlooked or underreported in the NF1 patient population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0119093PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364663PMC
March 2016

Clinical response to bevacizumab in schwannomatosis.

Neurology 2014 Nov 22;83(21):1986-7. Epub 2014 Oct 22.

From The Johns Hopkins Hospital (J.O.B., K.C.S., A.L.B., A.J.B.), Baltimore, MD; St. Mary's Hospital (D.G.E.), Manchester, UK; University of Alabama at Birmingham (B.K.); and NYU Langone Medical Center (D.Z., M.A.K.), New York.

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http://dx.doi.org/10.1212/WNL.0000000000000997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248457PMC
November 2014

Informed consent for exome sequencing research in families with genetic disease: the emerging issue of incidental findings.

Am J Med Genet A 2014 Nov 22;164A(11):2745-52. Epub 2014 Sep 22.

McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland.

Genomic sequencing technology is increasingly used in genetic research. Studies of informed consent for exome and genome sequencing (ES/GS) research have largely involved hypothetical scenarios or healthy individuals enrolling in population-based studies. Studies have yet to explore the consent experiences of adults with inherited disease. We conducted a qualitative interview study of 15 adults recently enrolled in a large-scale ES/GS study (11 affected adults, four parents of affected children). Our study had two goals: (1) to explore three theoretical barriers to consent for ES/GS research (interpretive/technical complexity, possibility of incidental findings, and risks of loss of privacy); and (2) to explore how interviewees experienced the consent process. Interviewees could articulate study goals and processes, describe incidental findings, discuss risks of privacy loss, and reflect on their consent experience. Few expected the study would identify the genetic cause of their condition. All elected to receive incidental findings. Interviewees acknowledged paying little attention to potential implications of incidental findings in light of more pressing goals of supporting research regarding their own medical conditions. Interviewees suggested that experience living with a genetic condition prepared them to adjust to incidental findings. Interviewees also expressed little concern about loss of confidentiality of study data. Some experienced the consent process as very long. None desired reconsent prior to return of study results. Families with inherited disease likely would benefit from a consent process in which study risks and benefits were discussed in the context of prior experiences with genetic research and genetic disease.
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http://dx.doi.org/10.1002/ajmg.a.36706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386622PMC
November 2014

Intracranial hemorrhage as the initial manifestation of a congenital disorder of glycosylation.

Pediatrics 2006 Aug 30;118(2):e514-21. Epub 2006 Jun 30.

McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Hospital, Children's Center, Johns Hopkins University School of Medicine, 600 N Wolfe St, Blalock 1008, Baltimore, Maryland 21205, USA.

Intracranial hemorrhage in a term neonate is a rare event in the absence of an identifiable precipitating factor such as severe thrombocytopenia, mechanical trauma, asphyxia, infections, or congenital vascular malformations. Congenital disorders of glycosylation are a genetically and clinically heterogeneous group of multisystem disorders characterized by the abnormal glycosylation of a number of glycoproteins. Although bleeding caused by abnormal glycosylation of various coagulation factors is a well-known clinical complication of several types of congenital disorders of glycosylation, intracranial hemorrhage has not been reported as an initial manifestation of this entity. Here we report the detailed history of a family with 2 consecutive male infants, both born at term with intracranial hemorrhage diagnosed within the first 24 hours of life. The diagnosis of a congenital disorder of glycosylation was established in the second infant by an abnormal glycosylation of serum transferrin detected by electrospray-ionization mass spectrometry. Both infants showed significant neurologic deterioration during the first month of life, and both died at 5 months of age. Intracranial hemorrhage in a term neonate without a potential precipitating factor represents yet another clinical feature that should raise the suspicion for a congenital disorder of glycosylation.
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http://dx.doi.org/10.1542/peds.2005-1307DOI Listing
August 2006