Aslı İnci1, Filiz Başak Cengiz Ergin2, Burcu Topcu Yüce2, Bahattin Çiftçi2, Ercan Demir3, Necla Buyan4, İlyas Okur2, Gürsel Biberoğlu2, Rıdvan Murat Öktem2, Leyla Tümer2, Fatih Süheyl Ezgü2. 1. Department of Pediatric Metabolism, Gazi University School of Medicine, 06500, Beşevler, Ankara, Turkey. aslid.inci@gmail.com. 2. Department of Pediatric Metabolism, Gazi University School of Medicine, 06500, Beşevler, Ankara, Turkey. 3. Department of Pediatric Neurology, Gazi University School of Medicine, 06500, Beşevler, Ankara, Turkey. 4. Department of Pediatric Nephrology, Gazi University School of Medicine, 06500, Beşevler, Ankara, Turkey.
Abstract
INTRODUCTION: Hypophosphatasia (HPP) is caused by mutations in the ALPL that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (ALP). Clinical manifestations range from extreme life-threatening lethal forms to no signs or symptoms at all. MATERIALS AND METHODS: Consecutive 30,000 outpatients and inpatients with ALP data were screened retrospectively, out of which 1000 patients were found to have low levels of ALP more than once. Then, patients were evaluated for the symptoms and signs of HPP with further biochemical and genetic analyses. RESULTS: Thirty-seven patients who had severe musculoskeletal pain, recurrent fractures, and tooth anomalies were then screened with substrate and DNA sequencing analyses for HPP. It was determined that eight patients had variants in the ALPL gene. A total of eight different ALPL variants were identified in eight patients. The variants, namely c.244G > C (p.Gly82Arg), c.1444C > T (p.His482Tyr), c.1487A > G (p.Asn493Ser), and c.675_676insCA (p.Met226GlnfsTer52), had not been previously reported. DISCUSSION: Considering the wide spectrum of clinical signs and symptoms, HPP should be among the differential lists of bone, muscle, and tooth abnormalities at any age.
INTRODUCTION:Hypophosphatasia (HPP) is caused by mutations in the ALPL that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (ALP). Clinical manifestations range from extreme life-threatening lethal forms to no signs or symptoms at all. MATERIALS AND METHODS: Consecutive 30,000 outpatients and inpatients with ALP data were screened retrospectively, out of which 1000 patients were found to have low levels of ALP more than once. Then, patients were evaluated for the symptoms and signs of HPP with further biochemical and genetic analyses. RESULTS: Thirty-seven patients who had severe musculoskeletal pain, recurrent fractures, and tooth anomalies were then screened with substrate and DNA sequencing analyses for HPP. It was determined that eight patients had variants in the ALPL gene. A total of eight different ALPL variants were identified in eight patients. The variants, namely c.244G > C (p.Gly82Arg), c.1444C > T (p.His482Tyr), c.1487A > G (p.Asn493Ser), and c.675_676insCA (p.Met226GlnfsTer52), had not been previously reported. DISCUSSION: Considering the wide spectrum of clinical signs and symptoms, HPP should be among the differential lists of bone, muscle, and tooth abnormalities at any age.
Authors: Jair Tenorio; Ignacio Álvarez; Leyre Riancho-Zarrabeitia; Gabriel Á Martos-Moreno; Giorgia Mandrile; Monserrat de la Flor Crespo; Mikhail Sukchev; Mostafa Sherif; Iza Kramer; María T Darnaude-Ortiz; Pedro Arias; Gema Gordo; Irene Dapía; Julián Martinez-Villanueva; Rubén Gómez; José Manuel Iturzaeta; Ghada Otaify; Mayte García-Unzueta; Alessandro Rubinacci; José A Riancho; Mona Aglan; Samia Temtamy; Mohamed Abdel Hamid; Jesús Argente; Víctor L Ruiz-Pérez; Karen E Heath; Pablo Lapunzina Journal: Am J Med Genet A Date: 2017-01-27 Impact factor: 2.802
Authors: Shelagh M Szabo; Ioannis C Tomazos; Anna Petryk; Lauren C Powell; Bonnie M K Donato; Yuri A Zarate; Anatoly Tiulpakov; Gabriel Ángel Martos-Moreno Journal: Orphanet J Rare Dis Date: 2019-04-25 Impact factor: 4.123