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Vitamin B6 challenge as a tool for detecting ALPL mutations and diagnosing hypophosphatasia
Sofía Alvarez1, Amelia Ocampo2, Patricia C Caso2
1Servicio de Medicina Interna, Hospital U.M. Valdecilla, Av Valdecilla sn, 39008, Santander, Spain.
None:
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.
