Genotype and clinical phenotype in congenital generalized lipodystrophy type 1: analysis and literature review

Abstract

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) inAGPAT2gene. 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:TheCGL1is 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,AGPAT2gene

CLC Number:

R723.2

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.

Figures/Tables4

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

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