Chapter title |
Apparent Acetaminophen Toxicity in a Patient with Transaldolase Deficiency
|
---|---|
Chapter number | 116 |
Book title |
JIMD Reports, Volume 44
|
Published in |
JIMD Reports, January 2018
|
DOI | 10.1007/8904_2018_116 |
Pubmed ID | |
Book ISBNs |
978-3-66-258616-7, 978-3-66-258617-4
|
Authors |
Jasmine Lee-Barber, Taylor E. English, Jacquelyn F. Britton, Nara Sobreira, Jason Goldstein, David Valle, Hans Tomas Bjornsson, Lee-Barber, Jasmine, English, Taylor E., Britton, Jacquelyn F., Sobreira, Nara, Goldstein, Jason, Valle, David, Bjornsson, Hans Tomas |
Abstract |
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 2.2.1.2), 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. 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. |
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