Clinical, biochemical and genetic spectrum of low alkaline phosphatase levels in adults.
Published
Journal Article
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 20-77yr) with unexplained low ALP levels. RESULTS: Nine had mild hyperphosphatemia and three had mild hypercalcemia. ALP levels were 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 had major health problems. Mutations in ALPL were found in 21 subjects (50%), including six novel mutations. All but one, were heterozygous mutations. Missense mutations were the most common (present in 18 subjects; 86%) and the majority were predicted to have a damaging effect on protein activity. The presence of a mutated allele was associated with tooth loss (48% versus 12%; p=0.04), slightly lower levels of serum ALP (p=0.002), higher levels of PLP (p<0.0001) and PEA (p<0.0001), as well as mildly 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 clinical manifestations are usually mild, in approximately 50% of the cases, enzyme activity is low enough to cause substrate accumulation and may predispose to defects in calcified tissues.
Full Text
Duke Authors
Cited Authors
- Riancho-Zarrabeitia, L; García-Unzueta, M; Tenorio, JA; Gómez-Gerique, JA; Ruiz Pérez, VL; Heath, KE; Lapunzina, P; Riancho, JA
Published Date
- April 2016
Published In
Volume / Issue
- 29 /
Start / End Page
- 40 - 45
PubMed ID
- 26783040
Pubmed Central ID
- 26783040
Electronic International Standard Serial Number (EISSN)
- 1879-0828
Digital Object Identifier (DOI)
- 10.1016/j.ejim.2015.12.019
Language
- eng
Conference Location
- Netherlands