Acute basal ganglia necrosis in the pediatric age group is a neurological disorder characterized by symmetrical degeneration of the caudate nucleus, putamen, and occasionally the globus pallidus. The outcome is less favorable for the familial cases where the course is relentlessly progressive or punctuated by recurrent episodes with involvement of additional brain regions and significant residual neurological damage. The differential diagnosis of the latter group includes mitochondrial respiratory chain defects organic acid disorders, Wilson disease, juvenile Huntington's chorea, pantothenate kinaseassociated neurodegeneration, biotin responsive basal ganglia disease, and the striatal necrosis associated with NUP62 mutation.
In this study we report on four siblings from a consanguineous Arab Muslim family who suffered from recurrent episodes of flaccid paralysis and encephalopathy and chronic progressive polyneuropathy associated with bilateral striatal necrosis. Using homozygosity mapping the pathogenic homozygous missense mutation c.373G>A was identified. This mutation alters a highly conserved glycine residue at position 125 to serine in the SLC25A19 gene which encodes the mitochondrial thiamine pyrophosphate transporter. SLC25A19 mutation was previously reported only in the Amish congenital lethal microcephaly but our patients' phenotype is markedly different with normal head circumference, early childhood development, and age-appropriate cognitive skills. Based on the role of SLC25A19 in mitochondrial thiamine transport, supplementation with high dose thiamine was initiated in all patients. Preliminary results suggest a favorable effect.
Our report suggests an allelic phenotype in SLC25A19 gene defects. Determination of the SLC25A19 sequence may be warranted in patients with bilateral striatal necrosis or progressive polyneuropathy.
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Spiegel, R., Shaag, A., Edvardson, S. et al. 827 Slc25A19 Mutation is a Novel Cause of Neuropathy and Bilateral Striatal Necrosis. Pediatr Res 68, 415 (2010). https://doi.org/10.1203/00006450-201011001-00827