尼曼-皮克病2例临床分析

Clinical analysis of two patients with Niemann-Pick disease

目的分析2例尼曼-皮克病(NPD)患儿(B型、C1型各1例)临床资料,探讨其骨髓细胞形态学表现及遗传学特征。方法2021年9月及2022年1月郑州大学第三附属医院诊治NPD患儿2例,分析其临床表现、酶学检测、肝胆胰脾超声检查、骨髓穿刺检查、基因检测结果及诊断、治疗、转归情况。结果2例患儿均因呼吸道症状就诊,无神经系统症状,体格检查及超声检查发现肝脾肿大,骨髓涂片可见泡沫细胞。患儿1血清酸性鞘磷脂酶水平降低,存在SMPD1基因c.7delC(p.Arg3Alafs*74)及c.926T>C(p.Leu309Pro)复合杂合突变,突变分别来自其父母,与NPD-B型相关;患儿2血清酸性鞘磷脂酶水平正常,存在NPC1基因c.2336dupT(p.Val780Argfs*9)及c.269C>G(p.Pro90Arg)复合杂合突变,突变分别来自其父母,与NPD-C1型相关。患儿1、2分别确诊为NPD-B型、NPD-C1型。NPD-B型患儿确诊后行脾脏半切除术,3个月后行异基因脐血干细胞移植,移植后1年随访肝脾无继续增大,智力、运动发育基本正常,无神经系统症状。NPD-C1型患儿确诊后口服麦格司他胶囊,口服2年后随访,肝脾肿大无缩小,智力正常,运动发育迟缓,无其他神经系统症状。结论对不明原因肝脾肿大患儿需警惕NPD,应尽早行酶学检测、骨髓穿刺检查及基因检测;骨髓泡沫细胞是NPD重要的诊断线索,确诊需行基因检测和酶学检测。

Objective To analyze the clinical data of Niemann-Pick disease(NPD)in two children(type B in 1 case and type Cl in 1),and to investigate the bone marrow cell morphology and genetic features.Methods Two children with NPD were diagnosed and treated in the Third Affiliated Hospital of Zhengzhou University from September 2021 to January 2022.The clinical manifestation,enzymaitc testing,ultrasound examination of liver,gallbladder,pancreas and spleen,bone marrow aspiration,genetic testing results,and diagnosis,treatment and outcome were analyzed.Results Two children consulted for respiratory symptoms,with no neurologic symptoms.The physical examination and ultrasonic examination revealed hepatosplenomegaly,and the bone marrow smear showed foam cells.In patient 1,the serum acid sphingomyelinase level decreased,and complex heterozygous mutations in SMPD1 gene c.7delC(p.Arg3Alafs*74)and c.926T>C(p.Leu309Pro)were obtained from her parents,respectively,which were associated with the NPD-B type.In patient 2,the serum acid sphingomyelinase level was normal,and complex heterozygous mutations in NPC1 gene c.2336dupT(p.Val780Argfs*9)and c.269C>G(p.Pro90Arg)were obtained from her parents,respectively,which were associated with the NPD-C1 type.The final diagnoses of patient 1 and 2 were NPD-B and NPD-C1,respectively.Patient 1 was subjected to partial splenectomy and subsequent allogeneic umbilical cord blood stem cell transplantation 3 months after surgery.Hepatosplenomegaly was controlled,the intelligence and motor development were basically normal,and there were no neurologic symptoms at one-year follow-up after transplantation.Patient 2 was given miglustat capsules after diagnosis.Hepatosplenomegaly was controlled,the intelligence was normal,the motor development was delay,and there were no other neurologic symptoms at two-year follow-up after medication.Conclusions NPD should be vigilant in children with unexplained hepatosplenomegaly,and enzymatic testing,bone marrow aspiration and genetic testing should be performed as soon as possible.Bone marrow foam cell is an important diagnostic clue for NPD,and the diagnosis requires genetic and enzymatic testing.