Abstract
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. 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. 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 (...Continue Reading
References
May 1, 1993·Bone and Mineral·J NapalJ González-Macías
Dec 1, 1996·The Journal of Clinical Endocrinology and Metabolism·K OzonoM Nakayama
Oct 22, 1998·European Journal of Human Genetics : EJHG·E MornetB Simon-Bouy
Jul 5, 2001·Human Mutation·A TaillandierE Mornet
Aug 2, 2001·Human Genetics·A S Lia-BaldiniE Mornet
Jun 20, 2003·Human Mutation·M SpentchianE Mornet
Aug 10, 2004·Prenatal Diagnosis·Ingrid WittersJean-Pierre Fryns
Jun 9, 2009·BMC Medical Genetics·Delphine FauvertEtienne Mornet
Apr 16, 2010·Annals of the New York Academy of Sciences·Michael P Whyte
Jan 27, 2011·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·F BarvencikM Amling
Apr 15, 2011·Annals of Human Genetics·Etienne MornetBrigitte Simon-Bouy
Feb 11, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Roger A L SuttonMichael P Whyte
Jan 29, 2013·Bone·Kathryn E BerksethRobert A Wermers
Feb 20, 2013·Bone·B EttingerR O Ritchie
Feb 22, 2013·The Journal of Bone and Joint Surgery. American Volume·Beatrice J EdwardsPaula H Stern
May 29, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Elizabeth ShaneMichael P Whyte
Aug 6, 2013·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·F E McKiernanJ Fuehrer
Oct 15, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Núria GuañabensMichael P Whyte
Jan 21, 2014·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Fergus Eoin McKiernanJay Fuehrer
Feb 27, 2014·European Journal of Human Genetics : EJHG·Christine HofmannBirgit Mentrup
Jul 16, 2014·The Journal of Biological Chemistry·Jérémie SilventJean-Yves Sire
Mar 5, 2015·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Tim CundyKlaus Klaushofer
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Citations
Nov 3, 2016·Bone·Birgit MentrupChristine Hofmann
Jan 28, 2017·American Journal of Medical Genetics. Part a·Jair TenorioPablo Lapunzina
Dec 14, 2017·Journal of Bone and Mineral Metabolism·Agnès TaillandierEtienne Mornet
May 5, 2018·Bioscience Reports·Lijun XuWeibo Xia
Sep 7, 2019·Calcified Tissue International·Nicola HeppJens-Erik Beck Jensen
Jul 4, 2019·Scientific Reports·Cristina García-FontanaManuel Muñoz-Torres
May 27, 2017·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·T SchmidtF Barvencik
Dec 4, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Nerea AlonsoStuart H Ralston
Feb 19, 2020·Orphanet Journal of Rare Diseases·C TorneroP Aguado
Feb 6, 2019·Journal of Bone and Mineral Metabolism·Frank RauchCheryl Rockman-Greenberg
Feb 8, 2020·Clinical Pediatric Endocrinology : Case Reports and Clinical Investigations : Official Journal of the Japanese Society for Pediatric Endocrinology·Toshimi MichigamiKeiichi Ozono
Sep 26, 2020·European Journal of Human Genetics : EJHG·Etienne MornetBrigitte Simon-Bouy
Apr 13, 2017·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·F E McKiernanI Rai
Jun 28, 2018·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·L López-DelgadoJ A Riancho
Sep 10, 2019·The Analyst·Zhiqiang ChenShufeng Liu
Mar 14, 2019·Archives of Endocrinology and Metabolism·Francisco Galeano-ValleRodolfo J Galindo
Dec 11, 2020·Bone·Robert DesboroughRichard Eastell
Oct 31, 2020·Journal of Cardiovascular and Thoracic Research·Behzad Zaker, Mohammadreza Ardalan
Mar 2, 2021·Bone·Anna PapadopoulouFotini Eleni Karachaliou
Feb 24, 2021·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·R Garcia-CarreteroJ-A Tenorio
Feb 20, 2021·Annals of Clinical Biochemistry·Mehmet Bilal AraciFerda Ozkinay
Sep 25, 2017·Metabolism: Clinical and Experimental·Etienne Mornet
Apr 15, 2021·Zeitschrift für Rheumatologie·P KarakostasV S Schäfer
Apr 13, 2021·Archives of Endocrinology and Metabolism·Lucio Henrique Rocha VieiraMiguel Madeira
Jul 1, 2021·JBMR Plus·Kenna KoehlerSteven Ing
Jul 15, 2021·Bone Reports·Nicola HeppJens-Erik Beck Jensen