Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism.

Neuromuscular Disorders : NMD
Natalie KellerMert Karakaya

Abstract

PDXK encodes for a pyridoxal kinase, which converts inactive B6 vitamers to the active cofactor pyridoxal 5'-phosphate (PLP). Recently, biallelic pathogenic variants in PDXK were shown to cause axonal Charcot-Marie-Tooth disease with optic atrophy that responds to PLP supplementation. We present two affected siblings carrying a novel biallelic missense PDXK variant with a similar phenotype with earlier onset. After detection of a novel PDXK variant using Whole Exome Sequencing, we confirmed pathogenicity through in silico protein structure analysis, determination of pyridoxal kinase activity using liquid chromatography-tandem mass spectrometry, and measurement of plasma PLP concentrations using high performance liquid chromatography. Our in silico analysis shows a potential effect on PDXK dimer stability, as well as a putative effect on posttranslational ubiquitination that is predicted to lead to increased protein degradation. We demonstrate that the variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels. Our patients' early diagnosis and prompt PLP replacement restored the PLP plasma levels, enabling long-term monitoring of clinical outcomes. We recommend that patients presenting with similar phen...Continue Reading

References

Mar 20, 1980·Nature·P M RichardsonA J Aguayo
Jan 1, 1993·Annual Review of Neuroscience·M E SchwabC E Bandtlow
Oct 3, 2003·The Journal of Biological Chemistry·Young Min JangOh-Shin Kwon
Jun 9, 2004·European Journal of Biochemistry·Jeong Han KangOh-Shin Kwon
Jun 11, 2004·Annual Review of Biochemistry·Andrew C Eliot, Jack F Kirsch
Apr 8, 2006·Journal of Structural Biology·Peng CaoTao Jiang
Jan 10, 2009·Brain Research·Michael P JankowskiKathryn M Albers
Apr 1, 2019·Biochimica Et Biophysica Acta. General Subjects·Rúben J RamosNanda M Verhoeven-Duif
May 19, 2019·American Journal of Medical Genetics. Part a·Mert KarakayaBrunhilde Wirth
Jun 13, 2019·Annals of Neurology·Viorica ChelbanUNKNOWN Care4Rare Canada Consortium and the SYNaPS Study Group

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Citations

Apr 30, 2021·Advances in Nutrition·Felix Hadtstein, Misha Vrolijk

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