Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Nov 19;34(2):261-266.
doi: 10.1515/jpem-2020-0139. Print 2021 Feb 23.

SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature

Francesco Porta  1 , Barbara Siri  1 , Nicoletta Chiesa  1 , Federica Ricci  2 , Lulash Nika  3 , Paola Sciortino  3 , Marco Spada  1
Affiliations
Review

SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature

Francesco Porta et al. J Pediatr Endocrinol Metab. .

Abstract

Objectives: Biallelic mutations in the SLC25A19 gene impair the function of the thiamine mitochondrial carrier, leading to two distinct clinical phenotypes. Homozygosity for the c.530G > C mutation is invariably associated to Amish lethal microcephaly. The second phenotype, reported only in 8 patients homozygous for different non-Amish mutations (c.373G > A, c.580T > C, c.910G > A, c.869T > A, c.576G > C), is characterized by bilateral striatal necrosis and peripheral polyneuropathy. We report a new patient with the non-Amish SLC25A19 phenotype showing compound heterozygosity for the new variant c.673G > A and the known mutation c.373G > A.

Case presentation: The natural history of non-Amish SLC25A19 deficiency is characterized by acute episodes of fever-induced encephalopathy accompanied by isolated lactic acidosis and Leigh-like features at magnetic resonance imaging (MRI). Acute episodes are prevented by high-dose thiamine treatment (600 mg/day). As shown in the new case, both mild clinical signs and basal ganglia involvement can precede the acute encephalopathic onset of the disease, potentially allowing treatment anticipation and prevention of acute brain damage. Peripheral axonal neuropathy, observed in 7 out of 9 patients, is not improved by thiamine therapy. In two early treated patients, however, peripheral neuropathy did not occur even on long-term follow-up, suggesting a potential preventive role of treatment anticipation also at the peripheral level.

Conclusions: Non-Amish SLC25A19 deficiency is an extra-rare cause of Leigh syndrome responsive to thiamine treatment. Ex adiuvantibus thiamine treatment is mandatory in any patient with Leigh-like features.

Keywords: SLC25A19; leigh syndrome; mitochondrial diseases; thiamine.

PubMed Disclaimer

References

    1. Manzetti, S, Zhang, J, van der Spoel, D. Thiamin function, metabolism, uptake, and transport. Biochemistry 2014;53:821–35. https://doi.org/10.1016/10.1021/bi401618y.
    1. Mkrtchyan, G, Aleshin, V, Parkhomenko, Y, Kaehne, T, Di Salvo, ML, Parroni, A, et al.. Molecular mechanisms of the non-coenzyme action of thiamin in brain: biochemical, structural and pathway analysis. Sci Rep 2015;5:12583. https://doi.org/10.1016/10.1038/srep12583.
    1. Marcé-Grau, A, Martí-Sánchez, L, Baide-Mairena, H, Ortigoza-Escobar, JD, Pérez-Dueñas, B. Genetic defects of thiamine transport and metabolism: a review of clinical phenotypes, genetics, and functional studies. J Inherit Metab Dis 2019;42:581–97. https://doi.org/10.1002/jimd.12125.
    1. Siu, VM, Ratko, S, Prasad, AN, Prasad, C, Rupar, CA. Amish microcephaly: long-term survival and biochemical characterization. Am J Med Genet 2010;7:1747–51. https://doi.org/10.1016/10.1002/ajmg.a.33373.
    1. Spiegel, R, Shaag, A, Edvardson, S, Mandel, H, Stepensky, P, Shalev, SA, et al.. SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis. Ann Neurol 2009;66:419–24. https://doi.org/10.1016/10.1002/ana.21752.

Substances