儿童单纯型甘油激酶缺乏症2例临床及遗传学分析

doi:10.12372/jcp.2025.24e0723

临床儿科杂志 ›› 2025, Vol. 43 ›› Issue (6): 458-463.doi: 10.12372/jcp.2025.24e0723

儿童单纯型甘油激酶缺乏症2例临床及遗传学分析

张利明¹, 刘磊², 杨建伟¹, 孙红启¹, 杨俊梅¹, 陈永兴³()

1.郑州大学附属儿童医院检验科郑州市儿童感染与免疫重点实验室（河南郑州 450018）
2.郑州大学附属儿童医院儿研所河南省儿童遗传代谢性疾病重点实验室（河南郑州 450018）
3.郑州大学附属儿童医院内分泌遗传代谢科（河南郑州 450018）

收稿日期:2024-07-17 录用日期:2024-10-23 出版日期:2025-06-15 发布日期:2025-06-01
通讯作者: 陈永兴电子信箱:cyx75@126.com
基金资助:
河南省重点研发专项(251111311300);河南省科技发展计划(232102311109);河南省儿童遗传代谢性疾病重点实验室开放课题(SS202205);河南省医学科技攻关计划联合共建项目(LHGJ20240560)

Clinical feature and genetic analysis of two children with isolation glycerol kinase deficiency

ZHANG Liming¹, LIU Lei², YANG Jianwei¹, SUN Hongqi¹, YANG Junmei¹, CHEN Yongxing³()

1. Department of Clinical Laboratory, Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan, China
2. Pediatric Medical Institute, Children's Hospital Affiliated to Zhengzhou University, Henan Provincial Key Laboratory for Genetic and Metabolic Disease in Children, Zhengzhou 450018, Henan, China
3. Department of Endocrine Genetics and Metabolism, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan, China

Received:2024-07-17 Accepted:2024-10-23 Published:2025-06-15 Online:2025-06-01

摘要/Abstract

摘要：

目的探讨2例单纯型甘油激酶缺乏症（GKD）患儿的临床表型和基因变异，以提高临床医师对该病的认识。方法收集2018年3月至2023年12月入院的2例单纯型GKD患儿的临床及基因检查资料，分析其临床特征和基因变异特点。结果 2例患儿均为男性，患儿1就诊时年龄为6岁7个月，表现为阵发性恶心呕吐，伴腹痛、纳差、精神差，存在反复低血糖、代谢性酸中毒、血中酮体和三酰甘油升高、尿中酮体、甘油浓度增高；患儿2就诊时年龄为3个月，出生后窒息、抽搐、昏迷、喂养困难，评估脑损伤住院治疗，发现血甘油三酯升高、尿甘油浓度增高。全外显子组基因检测发现患儿1的GK基因15号外显子存在1个c.1145C>T(p.A382V)半合子变异；患儿2的GK基因6号外显子存在1个c.422C>G(p.T141R)半合子变异，Sanger测序证实c.1145C>T和c.422C>G变异均来自表型正常的母亲，均被评级为临床意义未明，既往未见报道。结论单纯型GKD急性期表现缺乏特异性，血三酰甘油三酯和尿甘油浓度增高有助于诊断，确诊依赖于GK基因检测。

关键词: 甘油激酶缺乏症, 低血糖, GK基因, 三酰甘油, 儿童

Abstract:

Objective To investigate the clinical characteristics and genetic variations of two children with isolation glycerol kinase deficiency (GKD), fthereby enhancing clinicians' understanding of this the disease. Methods Clinical and genetic data were collected from two pediatric patients with isolated GKD admitted between March 2018 and December 2023.Their clinical manifestations and genetic variation profiles were analyzed systematically. Results Both patients were male. Patient 1 aged 6 years and 7 months, exhibited paroxysmal nausea, vomiting, abdominal pain, anorexia, and lethargy. Laboratory findings revealed recurrent hypoglycemia, metabolic acidosis, elevated blood ketone bodies and triglycerides, as well as increased urinary ketone bodies and glycerol concentrations. Patient 2 aged 3 months,experienced asphyxia, seizures, coma, and feeding difficulties shortly after birth, leading to hospitalization for brain injury assessment. Elevated blood triglycerides and increased urinary glycerol concentrations were detected.. The whole exon gene detection showed that there was a hemizygous variation c.1145C>T (p.A382V) in Exon 15 of GK gene in patient 1, and a hemizygous variation c.422C>G (p.T141R) in Exon 6 of GK gene in patient 2. Sanger sequencing confirmed that both the c.1145C>T and c.422C>G variants were from phenotypically normal mothers and classified as variants of uncertain significance according to the ACMG guidelines, with no prior reports. Conclusion The acute-phase symptoms of isolated GKD lack specificity. Elevated blood triglycerides and urinary glycerol concentrations can aid in diagnosis, while definitive diagnosis relies on GK gene testing.

Key words: glycerol kinase deficiency, hypoglycemia, GK gene, triglycerides, child

中图分类号:

张利明, 刘磊, 杨建伟, 孙红启, 杨俊梅, 陈永兴. 儿童单纯型甘油激酶缺乏症2例临床及遗传学分析[J]. 临床儿科杂志, 2025, 43(6): 458-463.

ZHANG Liming, LIU Lei, YANG Jianwei, SUN Hongqi, YANG Junmei, CHEN Yongxing. Clinical feature and genetic analysis of two children with isolation glycerol kinase deficiency[J]. Journal of Clinical Pediatrics, 2025, 43(6): 458-463.

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参考文献 34

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患儿	基因	染色体位置	转录本外显子	变异信息	纯合/杂合	正常人频率	蛋白功能预测	致病性分析	变异来源	是否报道
1	GK	chrX-30737626	NM_001205019； exon15	c.1145C>T (p.A382V)	半合子	-	有害	意义未明	母亲	否
2	GK	chrX:30694407-30694407	NM_000167.6； exon6	c.422C>G (p.T141R)	半合子	-	有害	意义未明	母亲	否

儿童单纯型甘油激酶缺乏症2例临床及遗传学分析

Clinical feature and genetic analysis of two children with isolation glycerol kinase deficiency

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