He Si-Jia, Li Dong-Jun, Lv Wen-Qiong, Tang Wen-Hao, Sun Shu-Wen, Zhu Yi-Ping, Liu Ying, Wu Jin, Lu Xiao-Xi
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Department of Pediatrics, Prenatal Diagnosis Center of West China Second University Hospital, Chengdu, China.
Front Pediatr. 2023 Jul 6;11:1199489. doi: 10.3389/fped.2023.1199489. eCollection 2023.
Mucolipidosis type II (MLII), or I-cell disease, is a rare lysosomal storage disease (LSD) caused by variants in the gene. MLII patients exhibit clinical phenotypes in the prenatal or neonatal stage, such as marked dysmorphic features, cardiac involvement, respiratory symptoms, dysostosis multiplex, severe growth abnormalities, and mental and motor developmental abnormalities. The median age at diagnosis for MLII is 0.7 years, the median survival is 5.0 years, and the median age at death is 1.8 years. No cure for MLII exists.
Sanger sequencing of the gene identified the compound heterozygous mutations c.673C > T in exon 7 and c.1090C > T in exon 9, which were novel double heterozygous mutations first reported in China. For the first time, we describe our experience in the use of HSCT for MLII. Our patient underwent HSCT with cells from a 9/10 human leukocyte antigen (HLA)-matched unrelated donor at 12 months of age. Myeloid neutrophil and platelet engraftment occurred on Days 10 and 11, respectively.
The patient's limb muscle tension was significantly reduced, and his gross and fine motor skills were improved four months after transplantation. DST(Developmental Screen Test) results showed that the patient's fine motor skills and mental development were improved compared with before HSCT.
MLII is a very severe lysosomal storage disease, to date, only 3 cases have been reported on the use of HSCT to treat MLII. Our data show that HSCT is a potential way to prolong the life of patients and improve their quality of life. Due to the lack of comparable data and time, the exact benefit remains unclear in MLII patients. Longer-term follow-up and in-depth prospective studies are indispensable.
II型粘脂贮积症（MLII），即I细胞病，是一种由该基因变异引起的罕见溶酶体贮积病（LSD）。MLII患者在产前或新生儿期就会出现临床表型，如明显的畸形特征、心脏受累、呼吸道症状、多发性骨发育异常、严重生长异常以及精神和运动发育异常。MLII的诊断中位年龄为0.7岁，中位生存期为5.0年，死亡中位年龄为1.8岁。目前尚无治愈MLII的方法。
对该基因进行桑格测序，鉴定出第7外显子的复合杂合突变c.673C>T和第9外显子的c.1090C>T，这是首次在中国报道的新型双杂合突变。我们首次描述了使用造血干细胞移植（HSCT）治疗MLII的经验。我们的患者在12个月大时接受了来自9/10人类白细胞抗原（HLA）匹配的无关供体的细胞进行HSCT。髓系中性粒细胞和血小板分别在第10天和第11天植入。
移植后4个月，患者肢体肌张力明显降低，粗大和精细运动技能得到改善。发育筛查测试（DST）结果显示，与HSCT前相比，患者的精细运动技能和智力发育有所改善。
MLII是一种非常严重的溶酶体贮积病，迄今为止，仅报道了3例使用HSCT治疗MLII的病例。我们的数据表明，HSCT是延长患者生命和提高其生活质量的一种潜在方法。由于缺乏可比数据和时间，MLII患者的确切获益尚不清楚。长期随访和深入的前瞻性研究不可或缺。
