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

Francesco Porta; Barbara Siri; Nicoletta Chiesa; Federica Ricci; Lulash Nika; Paola Sciortino; Marco Spada

doi:10.1515/jpem-2020-0139

Article

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

Francesco Porta , Barbara Siri , Nicoletta Chiesa , Federica Ricci , Lulash Nika , Paola Sciortino and Marco Spada

Published/Copyright: November 19, 2020

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 34 Issue 2

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: leigh syndrome; mitochondrial diseases; SLC25A19; thiamine

Corresponding author: Dr. Francesco Porta, MD, PhD, Department of Pediatrics, University of Torino, Piazza Polonia 94, 10126Torino, Italy, Phone: +39 011 6637777, Fax: +39 011 3135382, E-mail: francesco.porta@unito.it

Research funding: None declared.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Competing interests: None declared.

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Received: 2020-03-26

Accepted: 2020-10-04

Published Online: 2020-11-19

Published in Print: 2021-02-23

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Articles in the same Issue

https://doi.org/10.1515/jpem-2020-0139

Keywords for this article

leigh syndrome; mitochondrial diseases; SLC25A19; thiamine