TY - JOUR
T1 - Pyridoxal 5′-phosphate and related metabolites in hypophosphatasia
T2 - Effects of enzyme replacement therapy
AU - Akiyama, Tomoyuki
AU - Kubota, Takuo
AU - Ozono, Keiichi
AU - Michigami, Toshimi
AU - Kobayashi, Daisuke
AU - Takeyari, Shinji
AU - Sugiyama, Yuichiro
AU - Noda, Masahiro
AU - Harada, Daisuke
AU - Namba, Noriyuki
AU - Suzuki, Atsushi
AU - Utoyama, Maiko
AU - Kitanaka, Sachiko
AU - Uematsu, Mitsugu
AU - Mitani, Yusuke
AU - Matsunami, Kunihiro
AU - Takishima, Shigeru
AU - Ogawa, Erika
AU - Kobayashi, Katsuhiro
N1 - Funding Information:
This study was supported by the Japan Society for the Promotion of Science (Grant Number JP15K09622 ), the Japan Agency for Medical Research and Development , AMED (Grant Number 17ek0109135h0003 ), and a research grant from Alexion Pharmaceuticals . The authors confirm their independence from the sponsors; the content of the article was not influenced by the sponsors.
Funding Information:
T. Akiyama received a research grant and fees for lectures and advisory consultation from Alexion Pharmaceuticals, the manufacturer of asfotase alfa. T. Kubota received fees for lectures and advisory consultation from Alexion Pharmaceuticals. K. Ozono received fees for lectures and advisory consultation from Alexion Pharmaceuticals. T. Michigami received fees for lectures and advisory consultation from Alexion Pharmaceuticals. D. Kobayashi received a research grant from Alexion Pharmaceuticals. M. Noda received fees for lectures from Alexion Pharmaceuticals. N. Namba received fees for lectures and advisory consultation from Alexion Pharmaceuticals. Y. Mitani received a research grant from Alexion Pharmaceuticals.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - Asfotase alfa
KW - Diagnostic marker
KW - Liquid chromatography
KW - Therapeutic monitoring
KW - Vitamin B6
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U2 - 10.1016/j.ymgme.2018.07.006
DO - 10.1016/j.ymgme.2018.07.006
M3 - Article
C2 - 30049651
AN - SCOPUS:85050232027
SN - 1096-7192
VL - 125
SP - 174
EP - 180
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -
