Vitamin B6 challenge as a tool for detecting ALPL mutations and diagnosing hypophosphatasia
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 sensiti...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Cantabria (UC) |
| Repositorio: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unican.es:10902/38673 |
| Acceso en línea: | https://hdl.handle.net/10902/38673 |
| Access Level: | acceso abierto |
| Palabra clave: | Alkaline phosphatase Diagnosis Hypophosphatasia Pyridoxal phosphate Vitamin B6 |
| Sumario: | 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. |
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