About

Dr. Joshua L. Bonkowsky is a pediatric neurologist specializing in clinical care and research. He serves as a professor of Pediatrics at the University of Utah School of Medicine and is affiliated with Primary Children’s Hospital. Dr. Bonkowsky completed his undergraduate studies at Harvard College, followed by a Fulbright Fellowship in Vienna, Austria. He earned both his MD and PhD degrees from the University of California, San Diego. His residency training included pediatrics at the University of Utah and Children’s Hospital of Boston, as well as pediatric neurology at the University of Utah. Outside of his professional work, Dr. Bonkowsky enjoys camping with his daughter, building a quasi-functional radio telescope with his sons, and trail running.

Research topics

• Medicine
• Computer Science
• Psychiatry
• Genetics
• Intensive care medicine
• Engineering
• Internal medicine
• Software engineering
• Data science
• Biology
• Pathology
• Pediatrics

Selected publications

• BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy

  The American Journal of Human Genetics · 2026-03-25 · 1 citations

  article
  PublisherDOI

• Provider Perceptions of the Impact of Rapid Whole Genome Sequencing on Care and Management

  Research Square · 2026-04-10

  preprintOpen access
  PublisherOA PDFDOI

• Clinical risk factors predicting likelihood of pathogenic genetic result in NICU patients

  Genetics in Medicine Open · 2026-01-01

  articleOpen access1st authorCorresponding

  Purpose: Children with neonatal intensive care unit (NICU) admission have higher rates of genetic disease, but it is unclear which patients should have genetic testing. Our goal was to identify clinical predictors associated with a pathogenic genetic result in NICU infants. Methods: This was a retrospective, population-based cohort analysis of infants born between January 1, 2009 and June 30, 2011 with a history of NICU admission and subsequent follow-up and genetic testing through 2021. Results: A total of 99 infants met inclusion criteria. In total, 64 (65%) patients had a negative genetic test result; 35 (35%) had a positive (pathogenic) result. Lower birthweight, younger gestational age, longer length of stay, or 2 or more indicators of severe illness were associated with a pathogenic result. Conclusion: Our work suggests that clinical predictors can be used to guide genetic testing in NICU infants. Use of these clinical risk factors could provide a diagnostic care pathway, potentially shortening the diagnostic odyssey and reducing potential morbidities.

  PublisherDOI

• National Trends in MRI Screening and Transplant for US Adult Men With X-Linked Adrenoleukodystrophy

  Neurology Open Access · 2026-04-29

  articleSenior author
  PublisherDOI

• Message From the Editors to Our Reviewers

  Neurology Genetics · 2026-03-12

  articleOpen access
  PublisherDOI

• The Grey Zone Project: Risk‐Based Classification of <scp> <i>ABCD1</i> </scp> Variants in X‐Linked Adrenoleukodystrophy

  Journal of Inherited Metabolic Disease · 2026-02-09

  articleOpen access

  Newborn screening (NBS) for X-linked adrenoleukodystrophy (ALD) enables early identification of boys at risk for adrenal insufficiency (AI) and cerebral ALD (CALD). However, NBS frequently identifies ABCD1 variants of uncertain significance (VUS), which are associated with only borderline-elevated C26:0-lysophosphatidylcholine (LPC(26:0)) levels. Traditional American College of Medical Genetics and Genomics (ACMG) pathogenicity classification does not account for age-dependent penetrance or the broader phenotypic spectrum, complicating risk assessment and clinical management. Through the Grey Zone Project, we developed a risk-stratification framework using a receiver operating characteristic (ROC)-based approach prioritizing 95% sensitivity. This framework incorporates biochemical and longitudinal clinical data from 1627 control subjects and 196 confirmed ALD patients. Three pediatric risk categories were defined: "no ALD" (<110 nmol/L LPC(26:0)), "lower-risk AI/CALD" (110-177 nmol/L), and "at-risk AI/CALD" (>177 nmol/L). When applied to 108 samples carrying 51 unique ABCD1 VUSs, 26 variants were reclassified as "no ALD," 15 as "lower-risk AI/CALD," and 10 as "at-risk AI/CALD." The framework reclassifies ABCD1 variants based on biochemical risk profiles, reducing false-positive referrals, avoiding unnecessary MRI surveillance, and alleviating parental anxiety by identifying children who are unlikely to develop childhood-onset disease. Integrating biochemical thresholds with genetic and longitudinal clinical data improves the specificity of NBS without compromising its sensitivity. Providing systematic feedback on false-positive cases to screening laboratories will further refine cut-offs. This framework provides a scalable, evidence-based model for interpreting variants and enabling personalized follow-up in ALD and other disorders with a variable age of onset.

  PublisherOA PDFDOI

• Infant Outcomes, Risk Factors, and Diagnostic Yield After a Brief Resolved Unexplained Event

  JAMA Pediatrics · 2026-01-26 · 3 citations

  articleOpen access

  Importance: Since the introduction of the brief resolved unexplained event (BRUE) terminology, underpowered and conflicting research has led to persistent clinical uncertainty regarding the frequency of adverse outcomes, prognostic risk factors, and the diagnostic testing utility, contributing to wide practice variations. Objective: To (1) establish the frequency of serious underlying diagnoses and 3-month mortality after a BRUE in infants; (2) identify prognostic risk factors; and (3) quantify the diagnostic yield of common investigations. Data Sources: PubMed, Embase, Cochrane, and gray literature sources from January 2016 through July 2025. Study Selection: Cohort studies, case-control studies, and clinical trials of infants meeting 2016 American Academy of Pediatrics diagnostic criteria for BRUE. Data Extraction and Synthesis: Data were extracted by 1 reviewer and verified by a second. Random-effects meta-analyses were used to pool data. Grading of Recommendations Assessment, Development, and Evaluation was used to assess certainty in evidence. Main Outcomes and Measures: The primary outcomes were pooled prevalence of serious underlying diagnosis and 3-month cumulative mortality. Secondary outcomes included prognostic risk factors and diagnostic yield of specific tests. Results: From 664 citations, 24 studies (6603 infants) were included. The pooled prevalence of a serious underlying diagnosis was 6.0% (95% CI, 4.6%-7.9%; high certainty), and cumulative 3-month mortality was 1 death per 1851 infants (95% CI, 1 death per 597-5739 infants; moderate certainty). A history of multiple events (risk difference [RD], 3.7%; 95% CI, 1.7%-6.2%; high certainty) and prematurity (RD, 2.6%; 95% CI, 0.6%-5.2%; high certainty) were associated with increased risk of serious underlying diagnosis, while being aged 60 days or younger was not (RD, -0.5%; 95% CI, -2.7% to 3.0%; high certainty). Routine investigations were exceedingly low yield: metabolic panels had 0% yield (95% CI, 0%-0.5%; number needed to test [NNT] = 852; moderate certainty), electrocardiograms, 0.2% yield (95% CI, 0.0%-0.9%; NNT = 623; high certainty); and chest radiographs, 0.4% yield (95% CI, 0.2%-1.0%; NNT = 256; high certainty). Conclusions and Relevance: This systematic review and meta-analysis found that infant mortality after a BRUE was exceedingly rare, and a serious underlying diagnosis was present in a small but important group of infants; most routine diagnostic tests added little value and not infrequently had false-positive results. Clinical focus should therefore shift from blanket investigations to a targeted, risk-informed approach grounded in a few reliable higher-risk features. These findings provide a robust evidence basis for guideline revision.

  PublisherOA PDFDOI

• Consensus-Based Expert Recommendations for Diagnosis and Clinical Management of Vanishing White Matter

  Neurology · 2025-11-13 · 1 citations

  articleOpen access

  Vanishing white matter (VWM) is a rare disorder, characterized by degeneration of CNS white matter, clinically often exacerbated by stressors such as fever and minor head trauma. VWM is caused by biallelic pathogenic variants in the EIF2B1-5 genes, causing reduced activity of eukaryotic initiation of translation factor 2B, resulting in dysregulation of the integrated stress response (ISR). New scientific insights and increased clinical trials in experimental therapies highlight the need for clinical guidelines to improve and standardize care for patients with VWM worldwide. Standardized care is important for therapy development, as it lessens clinical variability of trial participants at study entry, enabling more sensitive evaluation of treatment outcomes. The aim of this study was to develop expert consensus-based recommendations for diagnosis and management of VWM. A real-time Delphi process with a multidisciplinary expert panel was conducted to formulate consensus-based recommendations. A literature review was performed to determine the strength of available evidence supporting each recommendation. The consensus yielded 43 recommendations on diagnosis, including genetic and MRI criteria, and on clinical management concerning disease progression, acute and long-term care, and preventive strategies. All known pathogenic and likely pathogenic EIF2B1-5 variants were identified from the literature and Amsterdam Leukodystrophy Center laboratory. An overview of these EIF2B1-5 variants was composed to facilitate diagnosis. Clinically used drugs may activate the ISR, posing a risk in VWM, or have no effect on or suppress the ISR, being probably safe in VWM. A second literature search explored the effects of clinically frequently used drugs on the ISR. Drugs were categorized into those likely to activate the ISR, suppress it, and have no likely effects on the ISR. Final judgment was achieved in a consensus meeting of experts. A patient management card was developed with input from clinical experts and patient advocates to provide information on these consensus-based recommendations in lay language and bridge the gap between scientific evidence and expert opinion on one side and the practical needs of clinicians and families on the other side. This study contributes to improving and standardizing VWM care based on scientific and expert insights, while highlighting key areas for future research.

  PublisherOA PDFDOI

• <i>ATAD1</i> Overexpression Enhances Mitochondrial and Peroxisomal Function in Zellweger Syndrome Disorder Models

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-15

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Zellweger Spectrum Disorders (ZSDs) are caused by mutations in any of the different peroxin (PEX) genes, which are essential for peroxisome biogenesis and function. Clinical features of ZSDs include seizures, leukodystrophy, renal and liver dysfunction, skeletal abnormalities, and they usually result in death during infancy or early childhood. There are no treatments for ZSDs, and their rarity, the large size of the PEX genes, and the numerous different genes, has impaired therapeutic development. We previously demonstrated that ATAD1, a mitochondrial protein quality control chaperone, could correct both mitochondrial and peroxisomal phenotypes in PEX3 patient fibroblasts. In this study, we investigated whether overexpressing ATAD1 could provide similar benefits in PEX1 and PEX6 patient cell lines, which account for over 70% of ZSD cases. We used established PEX6 -/- HEK293 cells, patient-derived fibroblasts with pathogenic PEX1 mutations, and newly created zebrafish mutants. Lipidomic profiling of the cell lines demonstrated widespread dysregulation, including accumulation of lysophosphatidylcholines with very-long-chain fatty acids, depletion of plasmalogens and cholesteryl esters containing polyunsaturated fatty acids, and a decrease in cardiolipins. Overexpressing ATAD1 partly corrected these imbalances, including normalizing VLCFA metabolism in PEX1 fibroblasts and restoring plasmalogens and cardiolipins in PEX6-deficient cells. Mitochondrial function analysis (Seahorse XF) showed that ATAD1 increased basal and ATP-linked respiration in both PEX1- and PEX6-deficient cells, sometimes surpassing the effects of PEX gene re-expression. ATAD1 increased peroxisome numbers in both PEX6 and PEX1 cells. Zebrafish Pex1 mutants exhibited impaired maximal respiration despite normal basal activity, confirming mitochondrial vulnerability in vivo. These findings further confirm a role for ATAD1 as a modifier that improves lipid metabolism, mitochondrial function, and peroxisome abundance that could function across multiple ZSDs.

  PublisherOA PDFDOI

• Identification of CNTN2 as a genetic modifier of PIGA-CDG in a family with incomplete penetrance and in Drosophila

  The American Journal of Human Genetics · 2025-02-12 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• NIH Grant DP2MH100008

  NIH · $2.2M · 2017

• NIH Grant R43OD023027

  NIH · $233k · 2018

• Development and Validation of a Zebrafish Model for Vanishing White Matter Disease

  NIH · $379k · 2018–2023

• NIH Grant K08DA024753

  NIH · $931k · 2014

• NIH Grant R21MH107039

  NIH · $410k · 2018

Frequent coauthors

• Adeline Vanderver

  University of Pennsylvania

  91 shared

• Rachel Palmquist

  University of Utah

  72 shared

• Tamara J. Stevenson

  University of Utah

  60 shared

• Geneviève Bernard

  McGill University

  58 shared

• Jacob Wilkes

  Intermountain Healthcare

  56 shared

• Marjo S. van der Knaap

  Emma Kinderziekenhuis

  50 shared

• Nicole I. Wolf

  Emma Kinderziekenhuis

  46 shared

• Florian Eichler

  Massachusetts General Hospital

  43 shared

Labs

• Bonkowsky LabPI

Education

• B.A.

  Harvard University

• Other

  University of California, San Diego