Wolman病临床及LIPA基因突变1例

目的 探讨Wolman病的临床特点及分子诊断的意义。方法 对1例符合Wolman病临床表现的患儿进行白细胞溶酶体酸性脂酶LIPA基因测序，分析其突变的类型。结果 约5月龄女婴，发现“皮肤黄染10余天，加重伴发热3 d”入院。查体见肝脾显著肿大，黄疸。实验室检查提示贫血，肝功能衰竭，高三酰甘油血症；X线胸腹片和腹部增强CT均提示特征性双侧肾上腺增大和广泛钙化。骨髓涂片可见海蓝色泡沫状组织细胞，PAS染色提示脂质沉积。DNA测序显示，LIPA基因编码区第7外显子上发生c.796G>T，p.G266*的纯合无义突变，导致266位甘氨酸（GGA）突变为终止密码（TGA）(p.G266*)，致溶酶体酸性脂酶缺失。结论 Wolman病婴儿期起病，以显著肝脾肿大、特征性双侧肾上腺增大和广泛钙化、高三酰甘油血症为特征，相应的酶学分析和LIPA基因检测均可确诊Wolman病。

One case with Wolman disease: clinical features and LIPA gene mutation

Objective Wolman disease (WD) is a rare autosomal recessive lysosomal storage disease, caused by deficiency of lysosomal acid lipase (LAL). In China, WD, the same type disorder as cholesteryl ester storage disease (CESD), but with severe clinical manifestations, is still poorly recognized. The purpose of this study was to investigate the clinical features, genetic abnormality of WD. Methods Clinical manifestations, laboratory examinations, and genetic testing of one case of WD were presented, analyzed, and discussed. The related literatures were reviewed. Results A approximately 5 month old female infant presented typical WD clinical features, including massive hepatosplenomegaly, remarkable jaundice, liver failure, severe coagulopathy, depressed bone marrow function, bilateral calcified adrenal glands, and in bone marrow aspirate, multiple foamy, vacuolated cytoplasm, sea blue histiocytes with negative periodic acid schiff staining were observed. Sequencing of the LIPA gene revealed that she was a homozygote with the nonsense mutation (c.796G>T) in exon 7, resulting in the change of amino acid 266 from Gly to termination codon (GGA TGA). This mutation finally result in a synthesis of the truncated protein (p.G266*). Conclusions The case presented here is the second WD case reported in mainland China. Based on the size of our population, WD and CESD are both underestimated. With the progress in DNA sequencing technique, and recognition the nature of WD and CESD, hopefully more cases will be diagnosed and recognized.