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

被引：19

作者：

Akiyama, Tomoyuki ^{[1
]}

Kubota, Takuo ^{[2
]}

Ozono, Keiichi ^{[2
]}

Michigami, Toshimi ^{[3
]}

Kobayashi, Daisuke ^{[4
]}

Takeyari, Shinji ^{[2
]}

Sugiyama, Yuichiro ^{[5
]}

Noda, Masahiro ^{[6
]}

Harada, Daisuke ^{[7
]}

Namba, Noriyuki ^{[7
]}

Suzuki, Atsushi ^{[8
]}

Utoyama, Maiko ^{[9
]}

Kitanaka, Sachiko ^{[10
]}

Uematsu, Mitsugu ^{[11
]}

Mitani, Yusuke ^{[12
]}

Matsunami, Kunihiro ^{[13
]}

Takishima, Shigeru ^{[14
]}

Ogawa, Erika ^{[15
]}

Kobayashi, Katsuhiro ^{[1
]}

机构：

[1] Okayama Univ, Dept Child Neurol, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[2] Osaka Univ, Dept Pediat, Grad Sch Med, Osaka, Japan

[3] Osaka Womens & Childrens Hosp, Dept Bone & Mineral Res, Osaka, Japan

[4] Hlth Sci Univ Hokkaido, Dept Food & Chem Toxicol, Sch Pharmaceut Sci, Tobetsu, Hokkaido, Japan

[5] Nagoya Univ, Dept Pediat, Grad Sch Med, Nagoya, Aichi, Japan

[6] Showa Gen Hosp, Dept Pediat, Tokyo, Japan

[7] JCHO, Dept Pediat, Osaka Hosp, Osaka, Japan

[8] Nagoya City Univ, Dept Neonatol & Pediat, Grad Sch Med Sci, Nagoya, Aichi, Japan

[9] Univ Miyazaki, Dept Pediat, Fac Med, Miyazaki, Japan

[10] Univ Tokyo, Dept Pediat, Grad Sch Med, Tokyo, Japan

[11] Tohoku Univ, Dept Pediat, Grad Sch Med, Sendai, Miyagi, Japan

[12] Kanazawa Univ Hosp, Dept Pediat, Kanazawa, Ishikawa, Japan

[13] Gifu Prefectural Gen Med Ctr, Dept Pediat, Gifu, Japan

[14] Soka Municipal Hosp, Dept Pediat, Saitama, Japan

[15] Nihon Univ, Dept Pediat & Child Hlth, Sch Med, Tokyo, Japan

来源：

MOLECULAR GENETICS AND METABOLISM | 2018年 / 125卷 / 1-2期

基金：

日本学术振兴会;

关键词：

Asfotase alfa; Liquid chromatography; Vitamin B6; Diagnostic marker; Therapeutic monitoring; CEREBROSPINAL-FLUID; 4-PYRIDOXIC ACID; CHILDREN; GENE;

D O I：

10.1016/j.ymgme.2018.07.006

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：174 / 180

页数：7

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