CAJ | 학술논문

目的探讨Wolman病的临床特点、酶学及分子诊断.方法对1例临床高度疑似Wolman病患儿进行白细胞溶酶体酸性酯酶测定及LIPA基因PCR扩增及PCR产物直接测序研究,回顾分析其临床、影像学及病理学特点.结果生后16 d男婴,因呕吐、腹胀、体重不增、肝脾肿大10d,疑似肠梗阻行剖腹探查术.腹部X线片及CT显示双侧肾上腺钙化.术中发现肝、脾、淋巴结肿大,其表面有黄色沉积物,小肠肿胀、僵硬.肝脏及淋巴结活检显示大量泡沫样细胞浸润.血清壳三糖苷酶572.78 nmol/( ml·h)[正常0～50 nmol/( ml·h)],白细胞溶酶体酸性酯酶3.5 nmol/( mg·h)[正常参考范围35.5 - 105.8 nmol/(mg·h)],LIPA基因突变分析发现第4外显子上c.318 ins T,p.Phe106fsX4纯合插入新突变,父母均为该突变携带者.结论 Wolman病以生后早期出现呕吐、腹胀、生长障碍、肝脾肿大及双侧肾上腺钙化为临床特点,腹部X线平片可见肾上腺钙化,白细胞溶酶体酸性酯酶缺乏,LIPA基因第4外显子上检出c.318insT,p.Phe106fsX4突变.
목적 탐토Wolman병적림상특점、매학급분자진단.방법 대1례림상고도의사Wolman병환인진행백세포용매체산성지매측정급LIPA기인PCR확증급PCR산물직접측서연구,회고분석기림상、영상학급병이학특점.결과 생후16 d남영,인구토、복창、체중불증、간비종대10d,의사장경조행부복탐사술.복부X선편급CT현시쌍측신상선개화.술중발현간、비、림파결종대,기표면유황색침적물,소장종창、강경.간장급림파결활검현시대량포말양세포침윤.혈청각삼당감매572.78 nmol/( ml·h)[정상0～50 nmol/( ml·h)],백세포용매체산성지매3.5 nmol/( mg·h)[정상삼고범위35.5 - 105.8 nmol/(mg·h)],LIPA기인돌변분석발현제4외현자상c.318 ins T,p.Phe106fsX4순합삽입신돌변,부모균위해돌변휴대자.결론 Wolman병이생후조기출현구토、복창、생장장애、간비종대급쌍측신상선개화위림상특점,복부X선평편가견신상선개화,백세포용매체산성지매결핍,LIPA기인제4외현자상검출c.318insT,p.Phe106fsX4돌변.
Objective To explore the clinical characteristics of Wolman disease and diagnostic methods using enzymatic and molecular analysis.Method Lysosomal acid lipase activity was measured using 4-methylumbelliferyl oleate in the leukocytes of an infant suspected of Wolman disease and LIPA gene mutational analysis was performed by PCR and direct sequencing in the proband and his parents.After the diagnosis was confirmed,the clinical,biochemical,radiological and histopathological findings in this case of Wolman disease were retrospectively reviewed.Result The sixteen-day-old boy was failing to thrive with progressive vomiting,abdominal distention and hepatosplenomegaly.Abdominal X-ray revealed adrenal calcifications which were confirmed on abdominal CT scan.Xanthomatosis were observed on enlarged liver,spleen and lymph nodes during abdominal surgery.Liver and lymph node biopsy showed foamy histiocytes.The lysosomal acid lipase activity in leukocytes was 3.5 nmol/( mg · h) [ contro1 35.5 - 105.8 nmol/( mg ·h) ].Serum chitotriosidase activity was 315.8 nmol/ ( ml · h) [ control 0 - 53 nmol/( ml · h) ].The patient was homozygote for a novel insert mutation allele c.318 ins T,p.Phe106fsX4 in exon 4 on LIPA gene.His both parents were carriers of the mutation.Conclusion The clinical features of Wolman disease include early onset of vomiting,abdominal distention,growth failure,hepatosplenomegaly and bilateral adrenal calcification after birth.A plain abdominal X-ray film should be taken to check for the typical pattern of adrenal calcification in suspected cases of Wolman disease.The enzymatic and molecular analyses of lysosomal acid lipase can confirm the diagnosis of Wolman disease.