婴儿型GM1神经节苷脂贮积症2例临床及遗传学特点

Clinical and genetic characteristics of 2 cases with infantile GM1 gangliosidosis

目的对2例婴儿型GM1神经节苷脂贮积症患儿临床及遗传学特点进行总结。方法收集2019年5月至6月天津市儿童医院康复科收治的2例婴儿型GM1神经节苷脂贮积症患儿临床资料,分析其临床及遗传学特点。结果2例患儿主要表现为婴儿期发病;精神运动发育落后,并有倒退;粗笨面容;对声音敏感;牙龈增厚;牙齿萌出异常;肌张力低下或肌张力障碍;骨发育不良;皮肤异常。例1肝脾大,角膜混浊,多发关节挛缩;例2眼底樱桃红斑,癫痫发作。生化检查均提示碱性磷酸酶显著增高,谷草转氨酶升高,谷丙转氨酶正常。头颅磁共振成像均示白质髓鞘化不良,例1还有丘脑对称性信号改变。全外显子二代测序发现,例1GLB1基因存在3p22.3(33137821-33138587)×1缺失突变,该片段缺失既往文献未见报道。结论婴儿型GM1神经节苷脂贮积症临床谱广泛。2例患儿均有皮肤异常,相对罕见。例1多发关节挛缩,尚未见文献报道,可能为新发表型。例1GLB1基因3p22.3(33137821-33138587)×1片段缺失为新突变,扩大了本病基因谱。

Objective To analyze clinical and genetic characteristics of 2 cases with infantile GM1 gang-liosidosis.Methods Clinical data of 2 cases with infantile GM1 gangliosidosis in the Department of Rehabilitation,Tianjin Children′s Hospital from May 2019 to June 2019 were retrospectively analyzed.Results The major manifestations of 2 cases included infantile onset,psychomotor retardation and retrogression,blundering face,sensitive to sound,gingival hyperplasia,abnormal eruption of teeth,hypotonia or dystonia,bone dysplasia,and skin abnormalities.Case 1 had hepatosplenomegaly,corneal opacity and multiple joint contractures.Case 2 had fundus cherry erythema and epileptic seizure.Biochemical results showed that alkaline phosphatase and aspartate transaminase significantly increased,and alanine transaminase was normal.Cranial nuclear magnetic imaging showed poor myelin sheath in the white matter in both cases,and case 1 also had symmetric signal changes in the thalamus.Whole exon sequencing showed that case 1 had deletion mutation of 3p22.3(33137821-33138587)×1 in the exon of GLB1 gene,which has not been previously reported.Conclusions The clinical spectrum of infantile GM1 gangliosidosis is broad.Both cases in this study have skin abnormalities,which are relatively rare.Multiple joint contractures in case 1 have not been previously reported,and considered as a new phenotype.The deletion mutation of 3p22.3(33137821-33138587)×1 in the exon of GLB1 gene in case 1 is a newly detected mutation,which expands the genetic profile of infantile GM1 gangliosidosis.