About

Sabrina W. Yum, M.D., is a Professor of Clinical Neurology and an Attending Neurologist at the Children's Hospital of Philadelphia. She serves as the Clinical Director of the CMTA Center of Excellence, co-Director of the Brachial Plexus Injury Program, and Interim Director of the Neuromuscular Program at Children's Hospital of Philadelphia. Her clinical expertise encompasses pediatric neurology, with a focus on pediatric neuromuscular diseases including SMA, DMD, BMD, LGMD, congenital myopathies, congenital myasthenic syndrome, and GBS. She is involved in gene therapy research for SMA and DMD and has a particular interest in Charcot-Marie-Tooth disease, nerve conduction studies, EMG, muscle ultrasound, and movement disorder treatments such as BOTOX injections. Her research centers on the biology and pathogenesis of connexin mutations associated with Charcot-Marie-Tooth disease and hearing loss, as well as the role of neurofilaments in axonal degeneration. Dr. Yum has contributed to understanding pediatric neuromuscular disorders through her clinical trials and research publications.

Research topics

• Medicine
• Pathology
• Surgery
• Pediatrics

Selected publications

• Real-world outcomes of delandistrogene moxeparvovec gene therapy: Motor outcomes and emerging safety concerns

  Molecular Therapy · 2025-10-05 · 3 citations

  articleOpen access
  PublisherOA PDFDOI

• Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo-controlled trial

  The Lancet Neurology · 2025-08-13 · 15 citations

  articleOpen access
  PublisherOA PDFDOI

• Charcot-Marie-Tooth disease type 1E: clinical natural history and molecular impact of <i>PMP22</i> variants

  Brain · 2025-06-06 · 2 citations

  articleOpen access

  Charcot-Marie-Tooth disease type 1E (CMT1E) is a rare, autosomal dominant peripheral neuropathy caused by missense variants, deletions, and truncations within the peripheral myelin protein-22 (PMP22) gene. CMT1E phenotypes vary depending on the specific variant, ranging from mild to severe, and there is little natural history and phenotypic progression data on individuals with CMT1E. Patients with CMT1E were evaluated during initial and follow-up visits at sites within the Inherited Neuropathy Consortium. Clinical characteristics were obtained from history, neurological exams, and nerve conduction studies. Clinical outcome measures were used to quantify baseline and longitudinal changes, including the Rasch-modified CMT Examination Score version 2 (CMTESv2-R) and the CMT Pediatric Scale (CMTPedS). The trafficking of PMP22 variants in transfected cells was correlated to disease severity. Twenty-four presumed disease-causing PMP22 variants were identified in 50 individuals from 35 families, including 19 missense variants, three in-frame deletions, and two truncations. Twenty-nine patients presented with delayed walking during childhood. At their baseline evaluation, the mean CMTESv2-R in 46 patients was 16 ± 7.72 (out of 32), and the mean CMTPedS from 17 patients was 28 ± 6.35 (out of 44). Six individuals presented with hearing loss, eleven with scoliosis, three with hip dysplasia, and one with both scoliosis and hip dysplasia. Twenty variants were localized within transmembrane domains; 31 of 35 individuals with these variants had moderate to severe phenotypes. Three variants were found in the extracellular domain and were associated with milder phenotypes. Reduced expression of PMP22 at the cell surface, and the location of missense variants within the transmembrane domain correlated with disease severity. Pathogenic PMP22 variants located within the transmembrane regions usually cause a moderate to severe clinical phenotype, beginning in early childhood, and have impaired trafficking to the plasma membrane.

  PublisherOA PDFDOI

• Hip Dysplasia in Patients with Charcot-Marie-Tooth Disease: Unraveling an Underrecognized Condition

  Journal of the Pediatric Orthopaedic Society of North America · 2024-07-01

  articleOpen access

  Background: Charcot-Marie-Tooth (CMT) hip disease is poorly understood, in part because the associated neuropathy may obfuscate symptoms, and little data exist to guide management or potential screening programs. The purpose of this study was to report our CMT hip experience from a single large tertiary care institution. Methods: A retrospective review of all patients diagnosed with CMT disease was performed after approval from our center's institutional review board. Patient demographic data were gathered from the electronic medical record. Patient presentation and physical exam findings were recorded, and all available radiographic imaging were reviewed for signs of hip pathology. When performed, details of surgical treatment were recorded. Descriptive statistics were performed to summarize pathology, characteristics, and procedural outcomes. Results: We identified 358 patients diagnosed with CMT, of which 96 patients (27%) had imaging of their hips. Of this subcohort, 20 (21%) had evidence of acetabular dysplasia (AD). This subcohort of CMT patients with confirmed AD was referred to orthopaedics at a mean age of 11 ± 6 years. Diagnosis of AD in CMT patients was most common between the ages of 10 and 16. Treatment often consisted of complete redirectional acetabular osteotomy. At a mean follow-up of 33 ± 28 months, symptomatic resolution was achieved in all but 2 hips (88%) with no significant complications. Conclusions: In our series, the incidence of AD among CMT patients with hip imaging was 21%. CMT patients were diagnosed with AD at 11 ± 6 years old, most commonly between the ages of 10 and 16. While the clinical presentation and age at presentation were variable, surgery (typically a complete redirectional osteotomy ± femoral derotation osteotomy) was generally successful, with the majority of patients achieving symptomatic resolution and a low complication rate at final follow-up. Key Concepts: (1)Charcot-Marie-Tooth (CMT) hip disease is poorly understood.(2)This study sought to report the rate of diagnosis and management of acetabular dysplasia in a CMT pediatric patient population at a single large tertiary care center.(3)While clinical presentation and age were variable, surgery was generally successful in the management of CMT hips. Level of Evidence: Level IV: case series.

  PublisherDOI

• Preemptive dual therapy for children at risk for infantile‐onset spinal muscular atrophy

  Annals of Clinical and Translational Neurology · 2024-05-31 · 4 citations

  articleOpen access

  OBJECTIVE: Compare efficacy of gene therapy alone (monotherapy) or in combination with an SMN2 augmentation agent (dual therapy) for treatment of children at risk for spinal muscular atrophy type 1. METHODS: Eighteen newborns with biallelic SMN1 deletions and two SMN2 copies were treated preemptively with monotherapy (n = 11) or dual therapy (n = 7) and followed for a median of 3 years. Primary outcomes were independent sitting and walking. Biomarkers were serial muscle ultrasonography (efficacy) and sensory action potentials (safety). RESULTS: Gene therapy was administered by 7-43 postnatal days; dual therapy with risdiplam (n = 6) or nusinersen (n = 1) was started by 15-39 days. Among 18 children enrolled, 17 sat, 15 walked, and 44% had motor delay (i.e., delay or failure to achieve prespecified milestones). Those on dual therapy sat but did not walk at an earlier age. 91% of muscle ultrasounds conducted within 60 postnatal days were normal but by 3-61 months, 94% showed echogenicity and/or fasciculation of at least one muscle group; these changes were indistinguishable between monotherapy and dual therapy cohorts. Five children with three SMN2 copies were treated with monotherapy in parallel: all sat and walked on time and had normal muscle sonograms at all time points. No child on dual therapy experienced treatment-associated adverse events. All 11 participants who completed sensory testing (including six on dual therapy) had intact sural sensory responses. INTERPRETATION: Preemptive dual therapy is well tolerated and may provide modest benefit for children at risk for severe spinal muscular atrophy but does not prevent widespread degenerative changes.

  PublisherOA PDFDOI

• 128P Non-coding DNA lipid nanoparticles elicit antitumor immune responses and synergize with anti-PDL1 antibodies in mouse models of hepatocellular carcinoma

  Immuno-Oncology Technology · 2024-12-01

  articleOpen access
  PublisherDOI

• Association of Body Mass Index With Disease Progression in Children With Charcot-Marie-Tooth Disease

  Neurology · 2023-06-28 · 4 citations

  articleOpen access

  BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the impact of body mass index (BMI) on disease progression over 2 years in children with Charcot-Marie-Tooth disease (CMT). METHODS: ). Disease severity was assessed using the CMT Pediatric Scale (CMTPedS), a clinical outcome assessment of disability (0-44 points, mild to severe). RESULTS: = 0.031). DISCUSSION: Children with CMT who were severely underweight, underweight, or obese exhibited greater disability at baseline. Over the 2-year period in those whose BMI remained stable, severely underweight children deteriorated at the fastest rate. For children who changed BMI categories over the 2 years, CMTPedS scores deteriorated faster in children who became overweight/obese. Interventions that maintain or improve BMI toward healthy weight may reduce disability in children with CMT.

  PublisherOA PDFDOI

• Ocular Biomarkers of Riboflavin Transporter Deficiency

  Journal of Neuro-Ophthalmology · 2022-08-02 · 5 citations

  article

  BACKGROUND: To describe the clinical presentation with a focus on ocular manifestations and response to riboflavin supplementation of 3 patients with riboflavin transporter deficiency (RTD) caused by mutations in SLC52A2 ( SLC52A2- RTD). METHODS: This is a retrospective review of records of 3 children (aged 18, n = 2 and age = 8, n = 1) with SLC52A2- RTD. Patients underwent comprehensive ophthalmic evaluations including color vision testing, pattern visual-evoked potentials (pVEPs, 1 patient) and spectral domain optical coherence tomography (SD-OCT) imaging. Patients received riboflavin supplements from the time of the molecular diagnosis of RTD. RESULTS: Two unrelated 18-year-old patients with SLC52A2- RTD had a symptomatic onset with sensorineural hearing loss and auditory neuropathy/dys-synchrony since age 3 and 11, respectively. On examination 7 years after symptomatic onset, they showed subnormal visual acuities (20/30 and 20/60, both eyes, respectively), preserved color vision, and a thin but measurable retinal ganglion cell layer (GCL) and nerve fiber (RNFL). The inner and outer nuclear layers were normal. The asymptomatic SLC52A2- positive brother of one of these patients started riboflavin supplementation right after the molecular diagnosis and had normal vision and SD-OCTs 7 years later. Onset of riboflavin supplementation in one of the 2 symptomatic cases resulted in acute improvement of the pattern visual-evoked potential and vision. CONCLUSIONS: Retinal ganglion cells and their axons are uniquely susceptible to RTD compared with other highly energy-dependent retinal neurons, such as photoreceptors, raising the possibility for alternative mechanisms of disease or protection. Riboflavin supplementation results in acute functional improvement of vision and long-term preservation of GCL and RNFL if initiated early.

  PublisherDOI

• Macrophage depletion blocks congenital SARM1-dependent neuropathy

  bioRxiv (Cold Spring Harbor Laboratory) · 2022-03-01 · 8 citations

  preprintOpen access

  ABSTRACT Axon loss contributes to many common neurodegenerative disorders. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. We identified two rare NMNAT2 missense variants in two brothers afflicted with a progressive neuropathy syndrome. The polymorphisms result in amino acid substitutions, V98M and R232Q, which reduce NMNAT2 NAD + -synthetase activity. We generated a mouse model of the human syndrome and found that Nmnat2 V98M / Nmnat2 R232Q compound-heterozygous CRISPR mice survive to adulthood but develop progressive motor dysfunction, peripheral axon loss, and macrophage infiltration. These disease phenotypes are all SARM1-dependent. Remarkably, macrophage depletion therapy blocks and reverses neuropathic phenotypes in Nmnat2 V98M/R232Q mice, identifying a SARM1-dependent neuroimmune mechanism as a key driver of disease pathogenesis. These findings demonstrate that SARM1 induces an inflammatory neuropathy and highlight the potential of immune therapy to treat this rare syndrome and other neurodegenerative conditions associated with NMNAT2 loss and SARM1 activation.

  PublisherOA PDFDOI

• Disease Progression in Charcot–Marie–Tooth Disease Related to <scp><i>MPZ</i></scp> Mutations: A Longitudinal Study

  Annals of Neurology · 2022-10-07 · 24 citations

  articleOpen access

  OBJECTIVE: The paucity of longitudinal natural history studies in MPZ neuropathy remains a barrier to clinical trials. We have completed a longitudinal natural history study in patients with MPZ neuropathies across 13 sites of the Inherited Neuropathies Consortium. METHODS: Change in Charcot-Marie-Tooth Examination Score (CMTES) and Rasch modified CMTES (CMTES-R) were evaluated using longitudinal regression over a 5-year period in subjects with MPZ neuropathy. Data from 139 patients with MPZ neuropathy were examined. RESULTS: The average baseline CMTES and CMTES-R were 10.84 (standard deviation [SD] = 6.0, range = 0-28) and 14.60 (SD = 7.56, range = 0-32), respectively. A mixed regression model showed significant change in CMTES at years 2-5 (mean change from baseline of 0.87 points at 2 years, p = 0.008). Subgroup analysis revealed greater change in CMTES at 2 years in subjects with axonal as compared to demyelinating neuropathy (mean change of 1.30 points [p = 0.016] vs 0.06 points [p = 0.889]). Patients with a moderate baseline neuropathy severity also showed more notable change, by estimate, than those with mild or severe neuropathy (mean 2-year change of 1.14 for baseline CMTES 8-14 [p = 0.025] vs -0.03 for baseline CMTES 0-7 [p = 0.958] and 0.25 for baseline CMTES ≥ 15 [p = 0.6897]). The progression in patients harboring specific MPZ mutations was highly variable. INTERPRETATION: CMTES is sensitive to change over time in adult patients with axonal but not demyelinating forms of MPZ neuropathy. Change in CMTES was greatest in patients with moderate baseline disease severity. These findings will inform future clinical trials of MPZ neuropathies. ANN NEUROL 2023;93:563-576.

  PublisherOA PDFDOI

Recent grants

• NIH Grant K08DC005394

  NIH · $953k · 2011

Frequent coauthors

• Mary M. Reilly

  National Hospital for Neurology and Neurosurgery

  756 shared

• Joshua Burns

  Sydney Children’s Hospitals Network

  741 shared

• Michael E. Shy

  University of Iowa

  726 shared

• Davide Pareyson

  Sydney Children’s Hospitals Network

  720 shared

• David N. Herrmann

  720 shared

• Matilde Laurá

  National Hospital for Neurology and Neurosurgery

  614 shared

• Steven S. Scherer

  University of Pennsylvania

  586 shared

• John Day

  Kaiser Permanente

  573 shared

Labs

• Yum LabPI