Evidence map›Paper›PMID 38959600›Full record

ArticleMolecular genetics and metabolism2024

Frontiers in congenital disorders of glycosylation consortium, a cross-sectional study report at year 5 of 280 individuals in the natural history cohort.

Christina Lam, Fernando Scaglia, Gerard T Berry, Austin Larson, Kyriakie Sarafoglou, Hans C Andersson, Evgenia Sklirou, Queenie K G Tan, Rodrigo T Starosta, Mustafa Sadek and 42 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics and metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

52 authors.

Christina LamDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA; Norcliffe Foundation Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA. Electronic address: ctlam2@uw.edu.
Fernando ScagliaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Joint BCM-CUHK Center of Medical Genetics, Prince of Wales Hospital, Hong KongSAR, China.
Gerard T BerryDivision of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Austin LarsonSection of Genetics, Department of Pediatrics, University of Colorado School of Medicine, USA.
Kyriakie SarafoglouDivisions of Endocrinology and Genetics-Metabolism, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA; Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, MN, USA.
Hans C AnderssonHayward Genetics Center, Dept Pediatrics Tulane School of Medicine, USA.
Evgenia SklirouDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Queenie K G TanDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Rodrigo T StarostaSection of Genetics, Department of Pediatrics, University of Colorado School of Medicine, USA.
Mustafa SadekDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Lynne WolfeMedical Genetic Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Seishu HorikoshiNorcliffe Foundation Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
May AliDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Rita BaroneChild Neuropsychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy; Research Unit of Rare Diseases and Neurodevelopmental Disorders, Oasi Research Institute, IRCCS, Troina, Italy.
Teresa CampbellDivision of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA.
Irene J ChangDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA; Division of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA.
Kiaira ColesChild Health Research Enterprise, Children's Hospital Colorado, USA.
Edward CookDivision of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, PA, USA.
Erik A EklundDepartment of Clinical Sciences, Lund University, Lund, Sweden; Department of Pediatrics, Skåne University Hospital, Lund, Sweden.
Nicole M EngelhardtDivision of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, PA, USA.
Mary FreemanDivision of Medical Genetics and Genomics, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, USA.
Jennifer FriedmanDivision of Neurosciences and Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA, USA; Rady Children's Institute for Genomic Medicine, San Diego, CA, USA; Rady Children's Hospital, San Diego, CA, USA.
Debbie Y T FuDivision of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Grace BotzoDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Brandy RawlsTexas Children's Hospital, Houston, TX, USA.
Christien HernandezChild Health Research Enterprise, Children's Hospital Colorado, USA.
Christin JohnsenDepartment of Pediatrics and Adolescent Medicine, University Medical Centre, Göttingen, Germany.
Kierstin KellerDivision of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, PA, USA.
Sara KramerPediatric Clinical Research Services, University of Minnesota, Minneapolis, MN, USA.
Bryce KuschelDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Angela LeshinskiDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Ivan Martinez-DunckerLaboratorio de Glicobiología Humana y Diagnóstico Molecular, Centro de Investigación en Dinámica Celular, Instituto de Investigación en Ciencias Básicas y Aplicadas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Mexico.
Gina L MazzaDivision of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, AZ, USA.
Saadet Mercimek-AndrewsDepartment of Medical Genetics, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Bradley S MillerDivision of Endocrinology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
Karthik MuthusamyDepartment of Clinical Genomics, Mayo Clinic, Jacksonville, FL, USA.
Juanita NeiraDepartment of Human Genetics, Emory University, Atlanta, GA 30322, USA.
Marc C PattersonDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN, USA; Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA; Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Natalie PogorelcPediatric Clinical Research Services, University of Minnesota, Minneapolis, MN, USA.
Lex N PowersDivision of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA.
Elizabeth RameyPediatric Clinical Research Services, University of Minnesota, Minneapolis, MN, USA.
Michaela ReinhartDivision of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, PA, USA.
Audrey SquireDivision of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA.
Jenny ThiesDivision of Genetic Medicine, Department of Pediatrics, Seattle Children's Hospital, Seattle, WA, USA.
Jerry VockleyDepartment of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States; Center for Rare Disease Therapy, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States.
Hayden VreugdenhilNorcliffe Foundation Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Peter WittersDepartment of Development and Regeneration, Katholieke Universiteit Leuven, 3000 Leuven, Belgium; Center for Metabolic Diseases, Department of Paediatrics, University Hospitals Leuven, Leuven, Belgium.
Mehdi YoubiDivision of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, PA, USA.
Aziza ZeighamiDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA.
Roni ZemetDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA.
Andrew C EdmondsonDivision of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, PA, USA.
Eva MoravaDivision of Medical Genetics and Genomics, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, USA.

Funding

Human Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6M
VISUAL INDICES OF NEUROTOXICITYP30ES001247 · NIEHS · UNIVERSITY OF ROCHESTER · PI Martha Susiarjo · 1985 to 2026
$42.8M
Pilot and Feasibility CoreU54NS115198 · NINDS · MAYO CLINIC ROCHESTER · PI MORAVA-KOZICZ, EVA · 2019 to 2023
$8.2M
NIEHS NIH HHS P30 ES001247NINDS NIH HHS U54 NS115198
6 · The paper itself

Abstract

objectiveOur report describes clinical, genetic, and biochemical features of participants with a molecularly confirmed congenital disorder of glycosylation (CDG) enrolled in the Frontiers in Congenital Disorders of Glycosylation (FCDGC) Natural History cohort at year 5 of the study.

methodsWe enrolled individuals with a known or suspected CDG into the FCDGC Natural History Study, a multicenter prospective and retrospective natural history study of all genetic causes of CDG. We conducted a cross-sectional analysis of baseline study visit data from participants with confirmed CDG who were consented into the FCDGC Natural History Study (5U54NS115198) from October 2019 to November 2023.

resultsThree hundred thirty-three subjects consented to the FCDGC Natural History Study. Of these, 280 unique individuals had genetic data available that was consistent with a diagnosis of CDG. These 280 individuals were enrolled into the study between October 8, 2019 and November 29, 2023. One hundred forty-one (50.4%) were female, and 139 (49.6%) were male. Mean and median age at enrollment was 10.1 and 6.5 years, respectively, with a range of 0.22 to 71.4 years. The cohort encompassed individuals with disorders of N-linked protein glycosylation (57%), glycosylphosphatidylinositol anchor disorder (GPI anchor) (15%), disorders of Golgi homeostasis, trafficking and transport (12%), dolichol metabolism disorders (5%), disorders of multiple pathways (6%), and other (5%). The most frequent presenting symptom(s) leading to diagnosis were developmental delay/disability (77%), followed by hypotonia (56%) and feeding difficulties (42%). Mean and median time between first related symptom and diagnosis was 2.7 and 0.8 years, respectively. One hundred percent of individuals in our cohort had developmental differences/disabilities at the time of their baseline visit, followed by 97% with neurologic involvement, 91% with gastrointestinal (GI)/liver involvement, and 88% with musculoskeletal involvement. Severity of disease in individuals was scored on the Nijmegen Progression CDG Rating Scale (NPCRS) with 27% of scores categorized as mild, 44% moderate, and 29% severe. Of the individuals with N-linked protein glycosylation defects, 83% of those with data showed a type 1 pattern on carbohydrate deficient transferrin (CDT) analysis including 82/84 individuals with PMM2-CDG, 6% a type 2 pattern, 1% both type 1 and type 2 pattern and 10% a normal or nonspecific pattern. One hundred percent of individuals with Golgi homeostasis and trafficking defects with data showed a type 2 pattern on CDT analysis, while Golgi transport defect showed a type II pattern 73% of the time, a type 1 pattern for 7%, and 20% had a normal or nonspecific pattern. Most of the variants documented were classified as pathogenic or likely pathogenic using ACMG criteria. For the majority of the variants, the predicted molecular consequence was missense followed by nonsense and splice site, and the majority of the diagnoses are inherited in an autosomal recessive pattern but with disorders of all major nuclear inheritance included. DISCUSSION: The FCDGC Natural History Study serves as an important resource to build future research studies, improve clinical care, and prepare for clinical trial readiness. Herein is the first overview of CDG participants of the FCDGC Natural History Study.

Indexed as

Congenital Disorders of GlycosylationAdolescentAdultChildChild, PreschoolCohort StudiesCross-Sectional StudiesFemaleGlycosylationHumansInfantMaleProspective StudiesRetrospective StudiesYoung AdultCDGCongenital disorders of glycosylationNatural historyNPCRS

Identifiers

PMID38959600
PMCPMC11299528

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