A fluorescent hydrazone exchange probe of pyridoxal phosphate for the assessment of vitamin B6 status.
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ABSTRACT:
SUBMITTER: Jun YW
PROVIDER: S-EPMC7061904 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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A fluorescent hydrazone exchange probe of pyridoxal phosphate for the assessment of vitamin B6 status.
Jun Yong Woong YW Hebenbrock Marian M Kool Eric T ET
Chemical communications (Cambridge, England) 20191201 2
Abnormal vitamin B6 status, marked by deficient intracellular concentrations of pyridoxal phosphate (PLP), is classified as a direct biomarker based on its biomedical significance. However, there exist no direct methods for measuring vitamin B6 status in intact cells. Here we describe the development of a fluorogenic probe, RAB6, which shows remarkable selectivity for PLP among the B6 vitamers and other cellular aldehydes. ...[more]
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Project description:IntroductionThe Vitamin B6-dependent epilepsies are a heterogeneous group of autosomal recessive disorders usually characterized by neonatal onset seizures responsive to treatment with vitamin B6 available as pyridoxine (PN) or as the biologically active form pyridoxal 5-phosphate (PLP). The vitamin B6-dependent epilepsies are caused by mutations in at least five different genes involved in B6 metabolism. A literature review revealed that only 30 patients with vitamin B6-dependent epilepsy caused by PLPBP mutation have been reported worldwide.Presentation of caseWe report a case of baby boy born to first-cousin Pakistani parents who presented with generalized as well as focal seizures starting a few hours after birth and responsive to PLP. Whole exome sequencing revealed a homozygous pathogenic variant NM_007198.4:c.46_47insCA, NP_009129.1:p.Leu17Hisfs, causing a CA duplication resulting in a frameshift in the PLPBP gene.DiscussionVitamin B6-Dependent Epilepsy due to PLPBP defect is a rare disorder. The developmental outcomes are variable even with early therapy. Few patients are reported to achieve optimal developmental milestones with therapy. PLP has been advocated as the treatment of choice for PLPBP defect, but oral PN has also demonstrated good seizure control in some patients, including ours.ConclusionVitamin B6-dependent epilepsy due to PLPBP defect is an important differential diagnosis to consider in patients with biochemical features suggestive of pyridoxamine 5'-phosphate Oxidase (PNPO) defect and gene testing can facilitate in reaching the correct diagnosis. Prompt diagnosis and treatment led to excellent seizure control in most patients.
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