儿童型低磷酸酶血症一例和基因突变分析

Hypophosphatase in children:a case report and gene mutation analysis

低磷酸酶血症(hypophosphatasia,HPP)是一种罕见的遗传性疾病,其特征是以骨及牙齿矿化缺陷,血清及骨碱性磷酸酶减低为主。该病的遗传方式为常染色体隐性或显性遗传,多数为常染色体隐性遗传,少数为显性遗传,发病率为1/10000,重型少见,轻型较常见[1]。由于家族内的可变表达和显性遗传方式的不完全外显,导致HPP临床表现差异较大,即从严重无骨骼矿化的死产到没有骨骼症状的早期牙齿脱落,根据年龄可分为6种形式:围生期型(致死性、良性),婴儿型,儿童型,成人型和牙型[2]。国外报道以围生期型和婴儿型为主[3],国内以儿童型和牙型为主,儿童型HPP的发病年龄在6月龄到18岁之间,症状严重程度不一[4]。笔者通过对1例儿童型HPP患儿的临床、生化、影像以及基因检测结果的分析来探讨HPP的诊断和发病机制。

Objective To further clarify the diagnosis and explore the genetic pathogenesis by clinical analysis and gene mutation detection in a child with hypoalkaline phosphatase(HPP).Methods Exome sequencing of the TNSALP gene showed that the child had a significantly lower blood alkaline phosphatase level and obvious skeletal deformities in the form of rickets-like changes.Results The changes in the reading frame and loss of the truncated protein(p.P519Afs*87)to a region important for enzymatic activity and bone mineralization were observed.Both parents of the affected children were phenotypically normal.Both carried a heterozygous mutation in c.1555-1561delinsGCTCAG,which was not detected in the elder sister and younger sister.Conclusions The common mutation loci at home and abroad are c.407G>A,C.251A>T,c.571G>A,c.1559delT,etc.The mutation loci is not reported in HGMDpro database.Further searches of Pubmed and ALPL gene mutation database show no report at home and abroad,so that this mutation is a new causative gene.