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

Authors

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

Published in

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. Jun 28, 2025. Epub Jun 28, 2025.

Abstract

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

PMID:
40579471
Bibliographic data and abstract were imported from PubMed on 28 Jun 2025.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.