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Homozygous mutation in the APOA1BP is associated with a lethal infantile leukoencephalopathy

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Abstract

Febrile-induced neurodegenerative diseases are a heterogeneous group of genetic disorders most commonly inborn errors of metabolism that result in irreversible damage involving the central nervous system. Here, we report on five siblings of consanguineous family who developed normally for the first 6–12 months of life then presented with a severe leukoencephalopathy following a trivial febrile illness. Using homozygosity mapping followed by whole exome sequencing, we identified a homozygous c. 281C>A mutation in the APOA1BP gene resulting in substitution of a highly conserved alanine residue with aspartic acid (p.Ala94Asp). APOA1BP encodes for epimerase that catalyzes the R to S epimerization of NAD(P)XH, a crucial step in the dehydration of these toxic metabolites accumulating during cellular metabolism. This is the first report of a defect in the nicotinamide nucleotide repair system in humans.

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Authors and Affiliations

  1. Pediatric Department B, Emek Medical Center, Afula, Israel

    Ronen Spiegel

  2. Genetic Institute, Emek Medical Center, Afula, Israel

    Stavit Shalev

  3. Rappaport faculty of Medicine, Technion, Haifa, Israel

    Ronen Spiegel & Stavit Shalev

  4. Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Avraham Shaag & Orly Elpeleg

Authors
  1. Ronen Spiegel
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  2. Avraham Shaag
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  3. Stavit Shalev
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  4. Orly Elpeleg
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Corresponding author

Correspondence to Ronen Spiegel.

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The authors declare that they have no conflict of interests.

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Spiegel, R., Shaag, A., Shalev, S. et al. Homozygous mutation in the APOA1BP is associated with a lethal infantile leukoencephalopathy. Neurogenetics 17, 187–190 (2016). https://doi.org/10.1007/s10048-016-0483-3

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  • DOI: https://doi.org/10.1007/s10048-016-0483-3

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