低磷酸酶血症治疗新进展

New progress in treatment of hypophosphatasia

低磷酸酶血症(HPP)是由编码组织非特异性碱性磷酸酶(TNSALP)的基因变异导致功能缺失引起的。HPP的症状、体征和并发症非常多变,包括骨骼低矿化、钙和磷酸盐代谢障碍、反复发生的骨折、疼痛、活动受限、牙齿过早脱落、生长发育迟缓和癫痫等。针对HPP有不同的治疗尝试,Asfotase alfa是一种骨靶向重组TNSALP,能够显著降低围生期和婴儿HPP患者的发病率和病死率,同时可改善生长发育、运动功能及生活质量。这种酶替代疗法耐受性良好,大多数不良反应为轻中度。现就近年来对该疾病的治疗新进展进行综述。

Hypophosphatasia(HPP)is caused by loss-of-function mutation(s)of the gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase(TNSALP).Its manifestations are variable,including impaired skeletal mineralization,altered calcium and phosphate metabolism,recurrent fractures,pain,impaired mobility,premature tooth loss,developmental delay,and seizures.There are different attempts for HPP.Asfotase alfa(Strensiq™),is a bone-targeted recombinant TNSALP which has shown significant improvements in morbidity and mortality in patients with perinatal and infantile hypophosphatasia,and it can improve growth,mobility function and quality of life.This enzyme replacement therapy has generally been well-tolerated,with most adverse reactions being mild-to-moderate in nature.This article reviews recent advances in the treatment of the disease.