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Case Reports
. 2023 Dec;191(12):2868-2872.
doi: 10.1002/ajmg.a.63376. Epub 2023 Aug 17.

Thiamine metabolism dysfunction syndrome 5 (THMD5) mimicking acute disseminated encephalomyelitis

Zachary E Thompson  1 , Natalie K Boyd  2 , Mellad M Khoshnood  2 , Jonathan D Santoro  2   3
Affiliations
Case Reports

Thiamine metabolism dysfunction syndrome 5 (THMD5) mimicking acute disseminated encephalomyelitis

Zachary E Thompson et al. Am J Med Genet A. 2023 Dec.

Abstract

Thiamine pyrophosphate (TPP), the substrate of Thiamine pyrophosphate kinase (TPK), is an important cofactor in carbohydrate metabolism, specifically as a cofactor of the Pyruvate dehydrogenase complex (PDH) complex. The nervous system is particularly dependent on TPP due to its reliance on glucose metabolism. In this case, a four-year-old girl had a previously unreported pathogenic variant of the gene encoding TPK (TPK1) which presented as Thiamine metabolism dysfunction syndrome 5 (THMD5; OMIM 614458). She had been diagnosed with acute disseminated encephalomyelitis and autism spectrum disorder (ASD), and initially presented with fever and agitation following vaccinations. After follow-up with genetic testing, our patient was found to have compound heterozygous pathogenic variants of TPK1. After treatment with biotin and thiamine her clinical status improved, and her ASD features resolved. The presentation of our patient was consistent with previous reports and adds to the evidence that thiamine and biotin are effective treatments of TPK1 related metabolic deficiencies. The improvement of neurobehavioral symptoms in this case was marked, highlighting the importance of early identification and therapeutic intervention in this condition.

Keywords: ADEM; TPK1; metabolic; mimic; thiamine.

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References

REFERENCES

    1. Banka, S., de Goede, C., Yue, W. W., Morris, A. A. M., von Bremen, B., Chandler, K. E., Feichtinger, R. G., Hart, C., Khan, N., Lunzer, V., Mataković, L., Marquardt, T., Makowski, C., Prokisch, H., Debus, O., Nosaka, K., Sonwalkar, H., Zimmermann, F. A., Sperl, W., & Mayr, J. A. (2014). Expanding the clinical and molecular spectrum of thiamine pyrophosphokinase deficiency: A treatable neurological disorder caused by TPK1 mutations. Molecular Genetics and Metabolism, 113(4), 301-306. https://doi.org/10.1016/j.ymgme.2014.09.010
    1. Bugiardini, E., Pope, S., Feichtinger, R. G., Poole, O. V., Pittman, A. M., Woodward, C. E., Heales, S., Quinlivan, R., Houlden, H., Mayr, J. A., Hanna, M. G., & Pitceathly, R. D. S. (2019). Utility of whole blood thiamine pyrophosphate evaluation in TPK1-related diseases. Journal of Clinical Medicine, 8(7), 991. https://doi.org/10.3390/jcm8070991
    1. Butterworth, R. F. (2003). Thiamin deficiency and brain disorders. Nutrition Research Reviews, 16(2), 277-284. https://doi.org/10.1079/NRR200367
    1. Dhir, S., Tarasenko, M., Napoli, E., & Giulivi, C. (2019). Neurological, psychiatric, and biochemical aspects of thiamine deficiency in children and adults. Frontiers in Psychiatry, 10, 207. https://doi.org/10.3389/fpsyt.2019.00207
    1. Fraser, J. L., Vanderver, A., Yang, S., Chang, T., Cramp, L., Vezina, G., Lichter-Konecki, U., Cusmano-Ozog, K. P., Smpokou, P., Chapman, K. A., & Zand, D. J. (2014). Thiamine pyrophosphokinase deficiency causes a Leigh disease like phenotype in a sibling pair: Identification through whole exome sequencing and management strategies. Molecular Genetics and Metabolism Reports, 1, 66-70. https://doi.org/10.1016/j.ymgmr.2013.12.007

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