Apparent Acetaminophen Toxicity in a Patient with Transaldolase Deficiency

  • Jasmine Lee-Barber
  • Taylor E. English
  • Jacquelyn F. Britton
  • Nara Sobreira
  • Jason Goldstein
  • David Valle
  • Hans Tomas BjornssonEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 44)


Transaldolase deficiency (MIM#: 606003) is a rare autosomal recessive defect in the pentose phosphate pathway. Affected individuals are at risk for progressive liver failure and hepatocarcinoma. In the transaldolase-deficient mouse model (Taldo1−/−), these hepatic complications are accentuated by oxidative stress related to acetaminophen administration. We report a 13-month-old transaldolase-deficient male who developed mild liver failure after receiving standard doses of acetaminophen during a febrile respiratory syncytial virus infection. He was admitted for respiratory distress with neutropenia and thrombocytopenia, but developed an enlarged nodular liver with accompanying splenomegaly and rising alpha-fetoprotein which peaked 2 weeks after acetaminophen exposure. Whole exome sequencing revealed compound heterozygous variants c.512_514delCCT (p.Ser171del) and c.931G > T (p.Gly311Trp) in TALDO1 (HGNC:11559), which encodes transaldolase (EC, a key enzyme in ribose metabolism. Urine polyols and plasma metabolomics confirmed the diagnosis of transaldolase deficiency. Studies on the Taldo1−/− mouse model demonstrate acetaminophen-induced liver failure can be prevented by administration of the antioxidant N-acetylcysteine. Moreover, a published report showed treatment of a transaldolase-deficient patient with N-acetylcysteine was associated with a decrease in alpha-fetoprotein levels. After discontinuation of acetaminophen and prior to initiation of N-acetylcysteine treatment, our patient demonstrated resolving alpha-fetoprotein levels suggesting acetaminophen incited the liver failure.

Conclusion: Our observations support the conclusion from mouse model studies that transaldolase-deficient patients are uniquely sensitive to acetaminophen and should avoid this antipyretic. Recognition of this individualized toxicity and avoidance of acetaminophen are essential for management of these patients.


Acetaminophen Actionable genetic disorders Pentose phosphate pathway Transaldolase deficiency Treatment of genetic diseases Whole exome sequencing 



The authors would like to thank the family for participating in this report. We thank Lisa Kratz at the Biochemical Genetics Laboratory at the Kennedy Krieger Institute for her reanalysis for specific metabolites in our patient’s sample. Dr. Bjornsson’s salary is covered by a NIH Director’s Early Independence Award (DP5OD017877). The Baylor-Hopkins Center for Mendelian Genomics is supported by a grant from the National Human Genome Research Institute, 1U54HG006493.


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Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2018

Authors and Affiliations

  • Jasmine Lee-Barber
    • 1
    • 2
  • Taylor E. English
    • 3
  • Jacquelyn F. Britton
    • 2
  • Nara Sobreira
    • 1
    • 2
  • Jason Goldstein
    • 4
  • David Valle
    • 1
    • 2
  • Hans Tomas Bjornsson
    • 1
    • 2
    • 5
    • 6
    Email author
  1. 1.Department of PediatricsThe Johns Hopkins UniversityBaltimoreUSA
  2. 2.McKusick-Nathans Institute of Genetic MedicineThe Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Russell H. Morgan Department of Radiology and Radiological ScienceThe Johns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Pavilion PediatricsLuthervilleUSA
  5. 5.Faculty of MedicineUniversity of IcelandReykjavíkIceland
  6. 6.Landspitali University HospitalReykjavíkIceland

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