About

Andrew C. Edmondson, MD, PhD, is an Assistant Professor of Pediatrics (Human Genetics) and an Attending Physician in the Division of Human Genetics and Metabolism at the Children's Hospital of Philadelphia. His research focuses on the biological roles of glycosylation in the brain, particularly in the context of rare genetic neurodevelopmental disorders known as Congenital Disorders of Glycosylation (CDG). His lab employs model systems such as primary cells, iPSCs, and mouse models to study how disruptions in glycosylation pathways affect neurological functions, including epilepsy, neurodevelopmental abnormalities, and neurodegeneration. Edmondson's work aims to elucidate the molecular mechanisms underlying these disorders and develop targeted therapeutics. He is also involved in discovering novel genetic syndromes related to glycosylation and exploring the functions of recently identified modifications like glycoRNA. With a strong commitment to diversity and mentorship, Edmondson actively mentors trainees and participates in initiatives promoting inclusive research and clinical translation.

Research topics

• Internal medicine
• Biology
• Pediatrics
• Genetics
• Medicine

Selected publications

• Expanded Clinical Spectrum of Autosomal-Dominant STT3A-CDG

  Biomolecules · 2026-03-12

  articleOpen access

  encodes the catalytic subunit of the oligosaccharyltransferase A (OST-A) complex and is classically linked to severe autosomal-recessive congenital disorder of glycosylation (CDG). To define the distinct autosomal-dominant disorder, we reviewed all published cases and integrated three previously unpublished individuals from the CDG natural history study. Across 21 individuals, abnormal transferrin glycosylation was present in nearly all individuals (20/21), and subtle facial dysmorphism was common (18/21). Neurodevelopmental involvement was frequent, including motor delay (13/21), learning difficulties (13/21), speech delay (12/21), and intellectual disability (10/21). Musculoskeletal manifestations were also common, including skeletal abnormalities (12/21), short stature (11/21), muscle cramps (8/21), and early-onset osteoarthritis in adults (6/21). Less frequent features included congenital heart defects (5/21) and coagulation factor deficiency (5/21). Importantly, the newly reported individuals expand dominant STT3A-CDG with previously unreported features, including anorectal malformation, morbid obesity, and clinically significant bleeding diathesis with von Willebrand factor and factor VIII deficiency. Biochemical signatures ranged from classic type I transferrin patterns to subtle or atypical abnormalities, emphasizing that near-normal transferrin testing does not exclude the diagnosis. Variants clustered in conserved catalytic regions, with recurrent p.Arg405 across de novo, inherited, and mosaic cases supporting a mutational hotspot and likely dominant-negative mechanism.

  PublisherOA PDFDOI

• L-fucose supplementation in a patient with global hypofucosylation and a mono-allelic variant in SLC35C1: Clinical improvement and assessment of biomarkers

  Molecular Genetics and Metabolism · 2026-01-08

  articleOpen access
  PublisherOA PDFDOI

• Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation

  Science Advances · 2026-04-15

  articleOpen access

  Diagnosing rare genetic diseases remains a major challenge despite widespread clinical testing. Long-read RNA sequencing (RNA-seq) offers a powerful approach to capturing the effects of genetic variants on the transcriptome, yet challenges with sequencing coverage, cost, tissue selection, and scalability have limited its clinical adoption. To address this, we developed STRIPE (Sequencing Targeted RNAs Identifies Pathogenic Events), a targeted long-read RNA-seq-based strategy for rare disease diagnosis and variant interpretation. STRIPE enables deep sequencing of full-length transcripts for any customized disease-specific gene panel such that a wide range of clinically informative readouts, including transcript aberrations and sequence variants, can be detected at haplotype-level resolution. Applying STRIPE to 88 individuals spanning two major rare disease groups, we accurately reidentified known pathogenic variants and revealed their transcript consequences, including many unexpected ones. For 8 of 15 splice site region variants, we observed more complex RNA processing defects beyond single exon skipping or cryptic splice site activation. Notably, we find that donor splice site variants frequently activate cryptic intronic polyadenylation sites, leading to premature transcript termination. Leveraging unique strengths of long-read RNA-seq, STRIPE also resolved variants of uncertain significance and uncovered disease-causing variants in five previously undiagnosed individuals. Overall, STRIPE is a powerful, adaptable, and scalable strategy with broad potential to improve clinical variant interpretation and advance genetic diagnosis of rare diseases.

  PublisherDOI

• Disease-specific growth charts capture characteristic growth patterns in children with PMM2 – CDG

  Molecular Genetics and Metabolism · 2026-04-20

  articleOpen access

  BACKGROUND: Growth faltering is prevalent in 96% of children with Phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG). Published long-term growth data is extremely limited. Growth and weight patterns of PMM2-CDG children differ from the general population limiting the utility of existing normative growth charts to track development trajectory in comparison to peers with PMM2-CDG. OBJECTIVE: Create PMM2-CDG disease-specific height-, weight-, and BMI-for-age reference growth charts (0-20 years). METHODS: De-identified growth data was provided by Frontiers in Congenital Disorders of Glycosylation Consortium, CDG Care, Minnesota Partnership for Biotechnology and Medical Genomics, and Glycomine, Inc. Semi-parametric modeling techniques were used to develop PMM2-CDG-specific charts along with nodal-point analyses for quantifying and examining PMM2-CDG growth differences relative to Centers for Disease Control (CDC) reference using one-sided quantile tests. RESULTS: Data of 156 children (females n = 75) with PMM2-CDG from 1614 visits were used to create height-, weight- and BMI-for-age growth curves. Median follow-up was 8.5 years (SD 4.5) for females and 6.8 years (SD 4.4) for males. CDG females were 13 cm shorter than their CDC reference peers at 20 years (150 vs 163 cm), and males were 16 cm shorter (160 vs 176 cm). All weight and height nodal points were significantly different (p < 0.05) at each age (4, 8, 12, 16, 20 years). CONCLUSION: PMM2-CDG specific reference charts can help enable the detection of deviations from peer growth patterns, aid in early detection of coexisting endocrinopathies, help guide treatment decisions and evaluate the effectiveness of new disease-modifying treatments in clinical trials.

  PublisherDOI

• Biochemical testing for congenital disorders of glycosylation: A technical standard of the American College of Medical Genetics and Genomics (ACMG)

  Genetics in Medicine · 2025-02-13 · 4 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• P075: A case of neuromyelitis optica spectrum disorder in ARCN1-related congenital disorder of glycosylation: A rare autoimmune phenotype

  Genetics in Medicine Open · 2025-01-01

  articleOpen accessSenior author
  PublisherDOI

• Expanding the phenotype of CARS1 variants to include congenital hyperinsulinism

  BMC Medical Genomics · 2025-10-21

  articleOpen access

  BACKGROUND: CARS1 loss of function compound heterozygous or homozygous variants have been reported in five individuals to cause a neurodevelopmental phenotype that includes microcephaly and brittle hair and nails. Additional multisystem involvement in these five people have included neurologic, cardiac, ophthalmologic and endocrine problems. CASE PRESENTATION: We report a sixth person with novel compound heterozygous variants in CARS1. In addition to the previously reported features such as intellectual disability, neurologic features, microcephaly and hair abnormalities, this patient had persistent hypoglycemia due to congenital hyperinsulinism. CONCLUSIONS: This report identifies two novel variants in CARS1 and expands the phenotype of this multisystem disorder to include congenital hyperinsulinism.

  PublisherOA PDFDOI

• Incidence and prevalence of phosphomannomutase 2-congenital disorder of glycosylation: Past, present, and future

  Molecular Genetics and Metabolism · 2025-07-15 · 3 citations

  articleOpen access1st authorCorresponding

  Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) accounts for about 60 % of all CDGs and is caused by pathogenic variants of the gene encoding PMM2, which catalyzes an essential early step in N-linked glycosylation. Efforts to derive an accurate prevalence estimate for this often life-threatening disorder, for which there are currently no approved therapies, are hampered by the wide spectrum of clinical manifestations, the rarity of the disease, and the lack of a central global patient registry. Here, we calculated new estimates of PMM2-CDG incidence and prevalence in North America and Europe based on the frequency of disease-causing alleles using the Hardy-Weinberg equation. Allele frequencies were obtained from the Genome Aggregation Database (gnomAD v4.0) and the likelihood of specific allele combinations resulting in a live birth was adjusted based on the occurrence of genotypes in patient datasets and the expected consequences for protein function. New incidence and prevalence estimates were then calculated in the context of historical ethnicity and birth data from national statistical databases, combined with estimated patient mortality rates. The calculated new incidence estimate was 1 in 33,576 for North America and Europe combined (1 in 40,375 and 29,043, respectively), which predicts an average of 303 live births per year for both regions combined since 1980. The new prevalence estimate was 1 in 63,694 (1 in 76,183 and 57,022 in North America and Europe, respectively), which translates to a total of 14,154 patients living with PMM2-CDG in North America and Europe. Notably, this prevalence is more than 5-fold higher than the current estimate of 2447 diagnosed cases combined, and 10-fold higher than the worldwide prevalence most frequently quoted in the literature. These striking differences highlight the underdiagnosis of the disease and the critical need for improved diagnostic and therapeutic strategies for PMM2-CDG.

  PublisherDOI

• Corrigendum to “Incidence and prevalence of phosphomannomutase 2-congenital disorder of glycosylation: Past, present, and future [Molecular Genetics and Metabolism 146 (2025) 109188]”

  Molecular Genetics and Metabolism · 2025-10-15

  erratumOpen access1st authorCorresponding
  PublisherDOI

• Novel mouse model reveals neurodevelopmental origin of PMM2-CDG brain pathology

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-03 · 2 citations

  preprintOpen access1st authorCorresponding

  Abstract Congenital disorders of glycosylation (CDG) are a group of neurogenetic conditions resulting from disruptions in the cellular glycosylation machinery. The majority of CDG patients have compound heterozygous pathogenic variants in the phosphomannomutase 2 ( PMM2) gene. Individuals with PMM2-CDG exhibit multi-systemic symptoms, prominently featuring neurological deficits with nearly all patients exhibiting cerebellar hypoplasia and ataxia. To overcome embryonic lethality caused by whole body knock-out of Pmm2 and mimic patient-related compound heterozygous pathogenic variants, we paired a Pmm2 flox allele ( Pmm2 fl ) with a catalytically inactive knock-in allele ( Pmm2 R137H ), commonly present in PMM2-CDG patients. Mice with post-mitotic loss of PMM2 from neurons or astrocytes are indistinguishable from unaffected littermates, including in a broad battery of neurological assessments. In contrast, removal of PMM2 from embryonic neural precursor cells leads to cerebellar hypoplasia, ataxia, seizures, and early lethality. Comprehensive multi-omics profiling, including metabolomics, glycomics, single-cell transcriptomics, proteomics, and glycoproteomics, reveal widespread molecular disturbances throughout the brain, with the cerebellum showing the most pronounced disruption. These findings highlight the heightened dependency of the developing cerebellum on intact N-glycosylation, aligning with clinical observations in PMM2-CDG patients. Importantly, glycoproteomic alterations identified in our mouse model are corroborated in PMM2-CDG patient post-mortem cerebellar tissue, underscoring the translational relevance of our findings and implicating impaired synaptic transmission as a key pathogenic mechanism.

  PublisherOA PDFDOI

Recent grants

• NIH Grant F30HL094050

  NIH · $86k · 2011

• O-glycosylation mechanisms of neurological deficits in congenital disorders of glycosylation

  NIH · $904k · 2020–2025

Frequent coauthors

• Daniel J. Rader

  University of Pennsylvania

  50 shared

• Éva Morava

  43 shared

• Muredach P. Reilly

  Columbia University Irving Medical Center

  36 shared

• Mingyao Li

  University of Pennsylvania

  35 shared

• Sekar Kathiresan

  Massachusetts General Hospital

  32 shared

• Nilesh J. Samani

  Glenfield Hospital

  25 shared

• Stephanie DerOhannessian

  25 shared

• Megan L. Wolfe

  Translational Therapeutics (United States)

  25 shared

Labs

• Edmondson LabPI

Education

• MD, PhD

  University of Pennsylvania

  2013