Clinical and molecular findings in children and young adults with persistent low alkaline phosphatase concentrations
Makaleler > Tam Makale · 2021
Yazarlar: Mehmet Bilal Araci, Bilcag Akgun, Tahir ATİK, Esra IŞIK, Ak Gunes, Burcu BARUTÇUOĞLU, Feriştah Ferda ÖZKINAY
ANNALS OF CLINICAL BIOCHEMISTRY, SCI Expanded İndekslerine Giren Dergi, Uluslararası, 2021
DOI: 10.1177/00045632211000102
Özet
Background<h2 class="title" style="box-sizing: inherit; clear: both; font-family: Merriweather, Georgia, Cambria, "Times New Roman", Times, serif; line-height: 2.4rem; margin-bottom: 1.2rem; margin-top: 3.6rem; font-size: 2rem; font-weight: 700; color: rgb(33, 33, 33); letter-spacing: normal;">Abstract</h2><div class="abstract-content selected" id="enc-abstract" style="box-sizing: inherit; clear: left; color: rgb(33, 33, 33); font-family: "system-ui", -apple-system, "Segoe UI", Roboto, Oxygen, Ubuntu, Cantarell, "Fira Sans", "Droid Sans", "Helvetica Neue", sans-serif; font-size: 16px;"><p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem;"><strong class="sub-title" style="box-sizing: inherit;">Background: </strong>Hypophosphatasia is a rare inherited metabolic disease resulted by <i style="box-sizing: inherit;">ALPL</i> gene mutations. It is characterized by defective bone and teeth mineralization. The phenotypic spectrum is highly variable ranging from lethal perinatal form to mild forms which are only diagnosed in adulthood or remain undiagnosed despite persistently low concentrations of ALP. The aim of this study is to evaluate the clinical phenotype and frequency of <i style="box-sizing: inherit;">ALPL</i> mutations in a group of patient with hypophosphatasaemia.</p><p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem;"><strong class="sub-title" style="box-sizing: inherit;">Methods: </strong>Thirty individuals with alkaline phosphatase values below 40 IU/L in at least two assessments and having no alternative explanation for their low ALP concentrations were included in the study. The clinical features and radiological data of the study group were re-investigated for hypophosphatasia-related findings. <i style="box-sizing: inherit;">ALPL</i> sequence analysis was performed using Sanger sequencing.</p><p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem;"><strong class="sub-title" style="box-sizing: inherit;">Results: </strong>No patient in the study group had severe symptoms, nor had they initially been diagnosed as having hypophosphatasia. Four different heterozygous <i style="box-sizing: inherit;">ALPL</i> mutations (c.542C>T, c.648 + 1G>A, c.657G>T and c.862 + 1G>C) were found in four patients. One splice site mutation (c.862 + 1G>C) was reported for the first time in this study.</p><p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem;"><strong class="sub-title" style="box-sizing: inherit;">Conclusion: </strong><i style="box-sizing: inherit;">ALPL</i> sequence analysis may help to diagnosing genetic defects in individuals with persistently low ALP concentrations and provide to take preventive measures before symptoms appear. As in the other populations, HPP displays allelic heterogeneity in our population.</p></div><p style="box-sizing: inherit; line-height: 1.5; margin-top: 1.2rem; margin-bottom: 1.2rem; color: rgb(33, 33, 33); font-family: "system-ui", -apple-system, "Segoe UI", Roboto, Oxygen, Ubuntu, Cantarell, "Fira Sans", "Droid Sans", "Helvetica Neue", sans-serif; font-size: 16px;"><strong class="sub-title" style="box-sizing: inherit;">Keywords: </strong>ALPL mutations; Hypophosphatasia; low serum alkaline phosphatase.</p>