先天性全身脂肪营养不良1型患者的基因型和临床表型分析及文献复习

doi:10.16150/j.1671-2870.2022.05.008

摘要/Abstract

摘要：

目的：分析先天性全身脂肪营养不良1型（congenital generalized lipodystrophy type 1, CGL1）患者的基因型和临床表型，提高临床对该疾病的认识。方法：分析1例因严重黑棘皮就诊的CGL1患儿的临床资料、实验室检查及基因检测结果，并结合现有文献报道的5例中国CGL1病例进行分析、总结。结果：患儿为10岁11个月的女性，临床表现为严重的黑皮棘伴有皮下脂肪减少。实验室检查显示高胰岛素血症、糖耐量异常、骨龄增大、脂联素降低、多囊卵巢。基因检测提示患儿存在AGPAT2基因复合杂合变异，c.646A>T:p.K216*（PVS1_Strong+ PM2+ PM3，来自父亲），c.406G>A:p.G136R（PM3_Strong+ PM1+ PM2+ PP3，来自母亲），2个位点均为可能致病的突变位点，在中国知网数据库中均未见该位点报道。文献复习显示，我国目前报道5例CGL1病例（其中男性2例，女性3例，年龄在66 d到26岁之间），所有患者均存在皮下脂肪减少，有2例患者存在较为严重的黑棘皮症状。结论：CGL1在我国人群中极为罕见，黑棘皮伴皮下脂肪减少需考虑此病，该病的精准诊断有赖于基因检测。

关键词: 黑棘皮, 先天性全身脂肪营养不良1型, AGPAT2基因

Abstract:

Objective: To explore the genotype and clinical phenotype of congenital generalized lipodystrophy type 1(CGL1), and to improve awareness of the disease. Methods: A patient with severe acanthosis nigricans was diagnosed as having CGL1, and the clinical information and results of laboratory and gene tests were analyzed. Five Chinese cases with CGL1 in the database were literaturally reviewed. Results: The patient was a girl(10 years and 11 months), who had significantly acanthosis nigricans and body subcutaneous fat loss. The examination of the girl showed hyperinsulinemia, impaired glucose tolerance, advanced bone age, low adiponectin and polycystic ovary. The compound heterozygous mutations were identified, which was c.646A>T:p.K216*(PVS1_Strong+ PM2+PM3 ( inherited from her father) and c.406G>A:p.G136R(PM3_Strong+PM1+PM2+PP3 (inherited from her mother) in AGPAT2 gene. The mutation of two gene loci could be pathogenic, which had not been reported in CNKI database. All 5 Chinese cases in CNKI database were reported before (including 2 males and 3 females, and age was between 66 days and 26 years old) showed the absence of adipose tissue, in which two patients presented severe acanthosis nigricans. Conclusions: The CGL1 is rare in Chinese population, and it should be considered as the patients present the acanthosis nigricans and absence of adipose tissue, and its diagnosis depends gene detection.

Key words: Acanthosis nigricans, Congenital generalized lipodystrophy type 1, AGPAT2 gene

中图分类号:

R723.2

宋宗先, 董治亚, 陆子文, 李彦晓, 陈烨. 先天性全身脂肪营养不良1型患者的基因型和临床表型分析及文献复习[J]. 诊断学理论与实践, 2022, 21(05): 592-597.

SONG Zongxian, DONG Zhiya, LU Ziwen, LI Yanxiao, CHEN Ye. Genotype and clinical phenotype in congenital generalized lipodystrophy type 1: analysis and literature review[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(05): 592-597.

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参考文献 19

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时间（min）	血糖（mmol/L）	胰岛素（μIU/mL）	C肽（μg/L）
0	4.49	66.03↑	5.07↑
30	6.70	379.00	14.60
60	8.07	577.70	19.44
120	9.08	>1 000	30.51
180	2.30	747.50	19.99

病例来源	Liu等^[6]	郭丹丹等^[4]	王怡萍等^[7]	孟源源等^[8]	张娟等^[9]	本例
报道年份	2019	2020	2020	2020	2021	2021
性别	男	男	女	女	女	女
年龄	16个月	66 d	4个月	12岁	26岁	10岁11个月
BMI(kg/m²)	18.3	15.4	15.8	17.1	21.8	19.8
主诉	发育迟缓	皮下结节、腹胀	体重增长慢	多尿，消瘦	糖尿病9年	黑棘皮
特殊面容	无	无	无	三角脸	无	无
脂肪萎缩肌肉明显	是	是	是	是	是	是
肝肿大	是	是	是	是	是	否
糖尿病	否	是	否	是	是	否
高甘油三酯症	是	是	否	是	是	否
胰岛素抵抗症状	无	无	无	黑棘皮，多毛	黑棘皮，多毛	黑棘皮，多毛
其他	无	皮下结节	无	右肾积水甲状腺多发胶质结节	卵巢囊肿肝血管瘤	骨龄大多囊卵巢
空腹血糖(mmol/L)	3.9	16.99	正常	13.5	升高	4.49
空腹胰岛素(μIU/mL)	-	-	正常	-	升高	66.03
空腹C肽(μg/L)	-	20.75	-	2.15	升高	5.07
糖化血红蛋白(%)	-	6.3	-	14.7	8.6	5.5
瘦素(ng/mL)	-	-	-	-	-	2.17
脂联素(g/mL)	-	-	-	-	-	0.28
AGPAT2突变位点	c.513delC / c.622_626del TCCTC	c.646A>T 纯合突变	c.335C>T/ c.792_805del GGAGAACGGGGCCA	c.379G>C/ c.317-10T>A	c.356_362del/ c.683T>C	c.646A>T/c.406G>A
氨基酸	Glu172Argfs81/ Ser208Leufs267	Lys216Ter	Pro112Leu/ Gln264Hisfs*208	Gly127Arg/splicing	Ala119fs/Leu228Pro	Lys216Ter/ Gly136Arg