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Early-onset progressive encephalopathy associated with NAXE gene variants: a case report of a Turkish child

  • Faruk IncecıkEmail author
  • Serdar Ceylaner
Letter to the Editor
  • 22 Downloads

Introduction

Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy (PEBEL) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration associated with a febrile illness. PEBEL is a lethal encephalopathy caused by NAXE gene mutations [1, 2].

The nicotinamide adenine dinucleotides (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) have essential roles in many cellular functions. NAD is involved in a series of catabolic reactions and in mitochondrial energy production, whereas NADP is a key component of numerous biosynthetic processes, as well as cellular antioxidant protection systems [3]. The nicotinamide ring within these cofactors is prone to hydration, forming NADHX or NADPHX, which can be present as R or S epimers and which can further degrade irreversibly to cyclic NAD(P)HX. NADHX can be slowly produced from NADH by GAPDH [4]. NAD(P)HX can also form spontaneously from the normal...

Notes

Funding

This study was not funded.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest regarding this article.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

References

  1. 1.
    Spiegel R, Shaag A, Shalev S, Elpeleg O (2016) Homozygous mutation in the APOA1BP is associated with a lethal infantile leukoencephalopathy. Neurogenetics 17:187–190CrossRefGoogle Scholar
  2. 2.
    Kremer LS, Danhauser K, Herebian D, Petkovic Ramadza D, Piekutowska-Abramczuk D, Seibt A et al (2016) NAXE mutations disrupt the cellular NAD(P)HX repair system and cause a lethal neurometabolic disorder of early childhood. Am J Hum Genet 99:894–902CrossRefGoogle Scholar
  3. 3.
    Houtkooper RH, Canto C, Wanders RJ, Auwerx J (2010) The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr Rev 31:194–223CrossRefGoogle Scholar
  4. 4.
    Rafter GW, Chaykin S, Krebs EG (1954) The action of glyceraldehyde-3-phosphate dehydrogenase on reduced diphosphopyridine nucleotide. J Biol Chem 208:799–811PubMedGoogle Scholar
  5. 5.
    Marbaix AY, Noel G, Detroux AM, Vertommen D, Van Schaftingen E, Linster CL (2011) Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair. J Biol Chem 286:41246–41252CrossRefGoogle Scholar
  6. 6.
    Marbaix AY, Tyteca D, Niehaus TD, Hanson AD, Linster CL, Van Schaftingen E (2014) Occurrence and subcellular distribution of the NADPHX repair system in mammals. Biochem J 460:49–58CrossRefGoogle Scholar
  7. 7.
    Prabhakar P, Laboy JI, Wang J, Budker T, Din ZZ, Chobanian M, Fahien LA (1998) Effect of NADH-X on cytosolic glycerol-3-phosphate dehydrogenase. Arch Biochem Biophys 360:195–205CrossRefGoogle Scholar
  8. 8.
    Yu D, Zhao FM, Cai XT, Zhou H, Cheng Y (2018) Clinical and genetic features of early-onset progressive encephalopathy associated with NAXE gene mutations. Zhongguo Dang Dai Er Ke Za Zhi 20:524–528PubMedGoogle Scholar

Copyright information

© Belgian Neurological Society 2019

Authors and Affiliations

  1. 1.Department of Pediatric NeurologyCukurova University Faculty of MedicineAdanaTurkey
  2. 2.InterGen Genetic Research CentreAnkaraTurkey

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