Clinical, biochemical and genetic spectrum of low alkaline phosphatase levels in adults
Background: Low serum levels of alkaline phosphatase (ALP) are a hallmark of hypophosphatasia. However, the clinical significance and the underlying genetics of low ALP in unselected populations are unclear. Methods: In order to clarify this issue, we performed a clinical, biochemical and genetic st...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universidad de Cantabria (UC) |
| Repositorio: | UCrea Repositorio Abierto de la Universidad de Cantabria |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.unican.es:10902/11023 |
| Acceso en línea: | http://hdl.handle.net/10902/11023 |
| Access Level: | acceso abierto |
| Palabra clave: | Alkaline phosphatase Hypophosphatasia Mutation analysis Pyridoxal phosphate Phosphoethanolamine ALPL |
| Sumario: | Background: Low serum levels of alkaline phosphatase (ALP) are a hallmark of hypophosphatasia. However, the clinical significance and the underlying genetics of low ALP in unselected populations are unclear. Methods: In order to clarify this issue, we performed a clinical, biochemical and genetic study of 42 individuals (age range 20–77 yr) with unexplained low ALP levels. Results: Nine hadmild hyperphosphatemia and three hadmild hypercalcemia. ALP levelswere inversely correlated with serum calcium (r = -0.38, p = 0.012), pyridoxal phosphate (PLP; r = -0.51, p = 0.001) and urine phosphoethanolamine (PEA; r = -0.49, p = 0.001). Although many subjects experienced minor complaints, such as mild musculoskeletal pain, none hadmajor health problems.Mutations in ALPL were found in 21 subjects (50%), including six novelmutations. All but one,were heterozygousmutations.Missensemutations were themost common (present in 18 subjects; 86%) and themajority were predicted to have a damaging effect on protein activity. The presence of amutated allelewas associated with tooth loss (48% versus 12%; p=0.04), slightly lower levels of serumALP (p=0.002), higher levels of PLP (p b 0.0001) and PEA (p b 0.0001), aswell asmildly increased serum phosphate (p=0.03). Ten individuals (24%) had PLP levels above the reference range; all carried a mutated allele. Conclusion: One-half of adult individuals with unexplained low serum ALP carried an ALPL mutation. Although the associated clinicalmanifestations are usuallymild, in approximately 50% of the cases, enzyme activity is lowenough to cause substrate accumulation and may predispose to defects in calcified tissues. |
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