探讨黏脂贮积症(ML)的临床表型及遗传学特点。

选择2016年6月至2023年6月于国家儿童中心复旦大学附属儿科医院确诊为ML的2例患儿(患儿1、2)为研究对象，回顾性分析其临床特征。分别以"黏脂贮积症""粘脂贮积症""儿童"与"mucolipidosis""children"为中、英文关键词，在中国知网(CNKI)、万方数据知识服务平台、PubMed数据库中，检索中国ML患儿相关文献，检索年限设定为2013年6月至2023年6月。本研究遵循的程序符合复旦大学附属儿科医院伦理委员会制定的标准，并获得该伦理委员会批准(批准文号：〔2022〕 241)。本研究纳入的ML患儿监护人对患儿的诊疗均知情同意，并签署知情同意书。

本研究2例患儿均为女性，年龄分别为1岁4个月和10岁，均表现为精神运动发育迟缓、手指畸形或异常。全外显子组基因测序(WES)结果显示，患儿1为GNPTAB基因纯合变异，患儿2为GNPTG基因复合杂合变异，2例患儿父母均为杂合携带者。根据本研究设定的检索策略，共检索到7篇中国学者发表的相关文献，共涉及15例ML中国患儿，纳入包括本研究在内的2例患儿，总计17例ML中国患儿。这17例患儿中，男、女性别比为1∶2.4，中位年龄为2.8岁(1.6～8.3岁)，中位身高为80.5 cm(76.5～123.0 cm)，中位体重为9.5 kg(8.6～26.0 kg)，GNPTAB基因突变率∶GNPTG基因突变率为13∶4，突变类型中，复合杂合变异∶纯合变异为9∶8。17例患儿均存在不同程度的人类表型本体论(HPO)临床异常表型，并且GNPTG基因突变者的年龄大于GNPTAB基因突变者。

ML作为一种罕见的遗传代谢性疾病，在我国以MLⅡ型、Ⅲ型为主(GNPTAB或GNPTG基因突变引起)，其中GNPTG基因突变ML患儿的生存期长于GNPTAB基因变异者。新生儿期基因筛查有助于ML的早期识别和干预。

To analyze and summarize clinical phenotypes and genetic characteristics of children with rare disease mucolipidosis (ML).

Two patients (patient 1 and patient 2) diagnosed with ML at the National Children′s Medical Center, Children′s Hospital of Fudan University, between June 2016 and June 2023 were selected as the study subjects. A retrospective analysis of their clinical characteristics was conducted. Literature related to Chinese pediatric ML cases was searched in China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and PubMed databases using the keywords " mucolipidosis" and " children" for the period from June 2013 to June 2023. The procedures followed in this study conformed to the standards set by the Ethics Committee of Children′s Hospital of Fudan University and were approved by the committee (Approval No. [2022] 241). Informed consent was obtained from the guardians of ML patients included in this study.

① Both patients were female, aged 1 year and 4 months, and 10 years, respectively, both exhibiting developmental delays and hand deformities or abnormalities. Whole exome sequencing (WES) revealed that patient 1 had a homozygous mutation in the GNPTAB gene, while patient 2 had compound heterozygous mutations in the GNPTG gene. Both sets of parents were heterozygous carriers. ②Based on the search strategy, 7 articles published by Chinese researchers were identified, involving 15 Chinese pediatric ML cases. Including the two patients from this study, a total of 17 cases were analyzed. Among the 17 patients, the male-to-female ratio was 1∶2.4, with an median age of 2.8 years (1.6-8.3 years), median height of 80.50 cm (76.45-123.00 cm), and median weight of 9.5 kg (8.6-26.0 kg). The distribution of different gene mutations was GNPTAB∶ GNPTG = 13∶4, and the mutation types was compound heterozygous∶homozygous = 9∶8. All 17 patients exhibited various degrees of clinical abnormalities as defined by the Human Phenotype Ontology (HPO), and patients with GNPTG mutations were older than those with GNPTAB mutations.

ML is a rare genetic metabolic disorder diagnosed mainly as ML type Ⅱ and Ⅲ in China, with mutations in the GNPTAB or GNPTG genes. Among these mutations, children with GNPTG gene variants tend to have a longer life expectancy than those with GNPTAB gene variants. Newborn genetic screening is helpful in identifying and intervening in ML at an early stage.