Pyridoxal 5'-phosphate and related metabolites in hypophosphatasia: Effects of enzyme replacement therapy

Mol Genet Metab. 2018 Sep;125(1-2):174-180. doi: 10.1016/j.ymgme.2018.07.006. Epub 2018 Jul 17.

Abstract

Objective: To investigate the utility of serum pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and 4-pyridoxic acid (PA) as a diagnostic marker of hypophosphatasia (HPP) and an indicator of the effect of, and patient compliance with, enzyme replacement therapy (ERT), we measured PLP, PL, and PA concentrations in serum samples from HPP patients with and without ERT.

Methods: Blood samples were collected from HPP patients and serum was frozen as soon as possible (mostly within one hour). PLP, PL, and PA concentrations were analyzed using high-performance liquid chromatography with fluorescence detection after pre-column derivatization by semicarbazide. We investigated which metabolites are associated with clinical phenotypes and how these metabolites change with ERT.

Results: Serum samples from 20 HPP patients were analyzed. The PLP-to-PL ratio and PLP concentration were elevated in all HPP patients. They correlated negatively with serum alkaline phosphatase (ALP) activity and showed higher values in more severe phenotypes (perinatal severe and infantile HPP) compared with other phenotypes. PL concentration was reduced only in perinatal severe HPP. ERT reduced the PLP-to-PL ratio to mildly reduced or low-normal levels and the PLP concentration was reduced to normal or mildly elevated levels. Urine phosphoethanolamine (PEA) concentration did not return to normal levels with ERT in most patients.

Conclusions: The serum PLP-to-PL ratio is a better indicator of the effect of ERT for HPP than serum PLP and urine PEA concentrations, and a PLP-to-PL ratio of <4.0 is a good indicator of the effect of, and patient compliance with, ERT.

Keywords: Asfotase alfa; Diagnostic marker; Liquid chromatography; Therapeutic monitoring; Vitamin B6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alkaline Phosphatase / blood
  • Alkaline Phosphatase / genetics*
  • Alkaline Phosphatase / therapeutic use
  • Child
  • Child, Preschool
  • Chromatography, High Pressure Liquid
  • Enzyme Replacement Therapy*
  • Ethanolamines / urine
  • Female
  • Humans
  • Hypophosphatasia / blood
  • Hypophosphatasia / drug therapy*
  • Hypophosphatasia / pathology
  • Hypophosphatasia / urine
  • Immunoglobulin G / genetics*
  • Immunoglobulin G / therapeutic use
  • Infant
  • Infant, Newborn
  • Male
  • Pyridoxal / blood
  • Pyridoxal Phosphate / blood*
  • Pyridoxic Acid / blood
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / therapeutic use
  • Vitamin B 6 / metabolism
  • Young Adult

Substances

  • Ethanolamines
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • Pyridoxal
  • Pyridoxic Acid
  • Pyridoxal Phosphate
  • phosphorylethanolamine
  • Vitamin B 6
  • Alkaline Phosphatase
  • asfotase alfa