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Summary <p>Low serum alkaline phosphatase is the biochemical hallmark of hypophosphatasia. However, it is a non-specific finding. Here we show that a 2-day vitamin B6 challenge is useful to identify carriers of <i>ALPL</i> gene mutations among patients with low serum alkaline phosphatase, with specificity and sensitivity over 90%.</p> Purpose <p>Hypophosphatasia (HPP) is a disorder characterized by deficient activity of the tissue non-specific alkaline phosphatase (ALP) isoenzyme, due to pathogenic variants of the <i>ALPL</i> gene. The biochemical hallmark of HPP is the reduced ALP activity in serum. Pyridoxal 5'-phosphate (PLP)<b>,</b> the major circulating form of vitamin B6, is a substrate of ALP. Thus, high PLP levels are commonly used as a diagnostic marker of HPP. This study aimed to assess the diagnostic utility of vitamin B6 supplementation for identifying patients with <i>ALPL</i> variants.</p> Patients and methods <p>We measured PLP in control subjects and patients with low serum ALP, with or without <i>ALPL</i> mutations, at baseline and after a 2-day or 6-day vitamin B6 supplementation (20&#xa0;mg per day of pyridoxine hydrochloride).</p> Results <p>Although mutation carriers tended to have higher PLP values, up to 33% had baseline levels within the normal range. The vitamin B6 challenge, particularly with the 2-day protocol, improved the diagnostic performance. After 2-day supplementation, all carriers had levels above 500&#xa0;nmol/l (sensitivity 100%; CI 95–100), whereas only 1 non-carrier surpassed that threshold (specificity 96%; CI 85–100).</p> Conclusion <p>A 2-day vitamin B6 supplementation test may be useful for identifying carriers of <i>ALPL</i> mutations among individuals with unexplained low serum ALP.</p>

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Vitamin B6 challenge as a tool for detecting ALPL mutations and diagnosing hypophosphatasia

  • 期刊论文

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  • 发表日期：

    2025年6月28日

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  • Sofía Alvarez,
  • Amelia Ocampo,
  • Patricia C. Caso,
  • Alvaro del Real,
  • Nuria Puente,
  • Ana I. Vega,
  • Leyre Riancho-Zarrabeitia,
  • María T. García-Unzueta,
  • José A. Riancho

摘要

Summary

Low serum alkaline phosphatase is the biochemical hallmark of hypophosphatasia. However, it is a non-specific finding. Here we show that a 2-day vitamin B6 challenge is useful to identify carriers of ALPL gene mutations among patients with low serum alkaline phosphatase, with specificity and sensitivity over 90%.

Purpose

Hypophosphatasia (HPP) is a disorder characterized by deficient activity of the tissue non-specific alkaline phosphatase (ALP) isoenzyme, due to pathogenic variants of the ALPL gene. The biochemical hallmark of HPP is the reduced ALP activity in serum. Pyridoxal 5'-phosphate (PLP), the major circulating form of vitamin B6, is a substrate of ALP. Thus, high PLP levels are commonly used as a diagnostic marker of HPP. This study aimed to assess the diagnostic utility of vitamin B6 supplementation for identifying patients with ALPL variants.

Patients and methods

We measured PLP in control subjects and patients with low serum ALP, with or without ALPL mutations, at baseline and after a 2-day or 6-day vitamin B6 supplementation (20 mg per day of pyridoxine hydrochloride).

Results

Although mutation carriers tended to have higher PLP values, up to 33% had baseline levels within the normal range. The vitamin B6 challenge, particularly with the 2-day protocol, improved the diagnostic performance. After 2-day supplementation, all carriers had levels above 500 nmol/l (sensitivity 100%; CI 95–100), whereas only 1 non-carrier surpassed that threshold (specificity 96%; CI 85–100).

Conclusion

A 2-day vitamin B6 supplementation test may be useful for identifying carriers of ALPL mutations among individuals with unexplained low serum ALP.