Bhadada Sanjay K, Pal Rimesh, Dhiman Vandana, Alonso Nerea, Ralston Stuart H, Kaur Simran, Gupta Rajat
Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India-160012.
Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, IGMM, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU.
Bone Rep. 2020 Jan 24;12:100247. doi: 10.1016/j.bonr.2020.100247. eCollection 2020 Jun.
Hypophosphatasia is an inborn error in metabolism characterized by low serum alkaline phosphatase (ALP) activity resulting from deactivating mutations in (also known as ), the gene that encodes the 'tissue-specific' isoenzyme of ALP. The disease exhibits significant clinical heterogeneity that spans from death to only dental complications in adult life. Herein, we report a 47-year-old woman presenting with fracture of shaft of left femur. She had been complaining of pain in both of her thighs for the past 3 years. In addition, she gave a history of premature loss of teeth. Review of old radiographs revealed pseudo-fractures involving the lateral cortices of the femora on both sides. Biochemical panel revealed hyperphosphatemia, persistently low total alkaline phosphatase (ALP) and low-normal bone turnover markers. Screening of her siblings revealed low ALP in her younger sister and brother who were otherwise free from any major dento-arthro-osseous complaints. Sanger sequencing showed a novel, heterozygous, missense mutation in exon 5 at position 311 (c.311a > g;p.104 Asn > Ser) of gene in the three members. The patient underwent open reduction and intramedullary nailing of left femur along with prophylactic nailing on right side. This case report represents the first genetically confirmed kindred of adult hypophosphatasia from the Indian subcontinent.
低磷性骨软化症是一种先天性代谢紊乱疾病，其特征是血清碱性磷酸酶（ALP）活性降低，这是由于编码ALP“组织特异性”同工酶的基因（也称为 ）发生失活突变所致。该疾病表现出显著的临床异质性，从死亡到仅在成年期出现牙齿并发症不等。在此，我们报告一名47岁女性，她因左股骨干骨折前来就诊。在过去3年里，她一直抱怨双侧大腿疼痛。此外，她有过早掉牙的病史。回顾旧的X光片发现双侧股骨外侧皮质有假性骨折。生化检查显示高磷血症、总碱性磷酸酶（ALP）持续偏低以及骨转换标志物处于低正常水平。对她的兄弟姐妹进行筛查发现，她的妹妹和弟弟碱性磷酸酶水平较低，但无任何主要的牙关节骨相关症状。桑格测序显示这三名家庭成员的 基因第5外显子311位（c.311a>g；p.104 Asn>Ser）存在一种新的杂合错义突变。该患者接受了左股骨切开复位髓内钉固定术，并对右侧进行了预防性髓内钉固定。本病例报告代表了印度次大陆首例经基因确诊的成人低磷性骨软化症家族病例。
