SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis

Authors

  • Ronen Spiegel MD,

    1. Department of Human Genetics and Metabolic Diseases, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
    2. Pediatric Department A, Ha'Emek Medical Center, Afula, Israel
    3. Genetic Institute, Ha'Emek Medical Center, Afula, Israel
    4. Rappaport School of Medicine, Technion, Haifa, Israel
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  • Avraham Shaag PhD,

    1. Department of Human Genetics and Metabolic Diseases, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
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  • Simon Edvardson MD,

    1. Pediatric Neurology Unit, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
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  • Hanna Mandel MD,

    1. Rappaport School of Medicine, Technion, Haifa, Israel
    2. Metabolic Unit, Mayer Medical Center, Rappaport School of Medicine, Technion, Haifa, Israel
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  • Polina Stepensky MD,

    1. Department of Human Genetics and Metabolic Diseases, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
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  • Stavit A. Shalev MD,

    1. Genetic Institute, Ha'Emek Medical Center, Afula, Israel
    2. Rappaport School of Medicine, Technion, Haifa, Israel
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  • Yoseph Horovitz MD,

    1. Pediatric Department A, Ha'Emek Medical Center, Afula, Israel
    2. Rappaport School of Medicine, Technion, Haifa, Israel
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  • Ophry Pines PhD,

    1. Department of Microbiology and Molecular Genetics, Institute of Medical Research (IMRIC), Hebrew University, Jerusalem, Israel
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  • Orly Elpeleg MD

    Corresponding author
    1. Department of Human Genetics and Metabolic Diseases, Hadassah–Hebrew University Medical Center, Jerusalem, Israel
    • Department of Human Genetics and Metabolic Diseases, Hadassah–Hebrew University Medical Center, Jerusalem 91120, Israel
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  • Potential conflict of interest: Nothing to report.

Abstract

Four patients, aged 7–20 years, suffered from recurrent episodes of flaccid paralysis and encephalopathy associated with bilateral striatal necrosis and chronic progressive polyneuropathy. Using homozygosity mapping, a pathogenic missense mutation in the SLC25A19 gene that encodes the mitochondrial thiamine pyrophosphate transporter was identified. An SLC25A19 mutation was previously reported in Amish congenital lethal microcephaly but the present patients' phenotype is markedly different, with normal head circumference, normal early childhood development, age-appropriate cognitive skills, and normal urinary organic acid profile. Determination of the SLC25A19 sequence should be considered in patients with bilateral striatal necrosis and progressive polyneuropathy. Ann Neurol 2009;66:419–424

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