Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene
Objective: Our study aims to summarize and analyze the clinical characteristics of transient infantile hypertriglyceridemia (HTGTI) and variants in the glycerol-3-phosphate dehydrogenase 1 (GPD1) gene and the effect of HTGTI on the protein structure of GPD1.Methods: Retrospective analysis, using the...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.916672/full |
| _version_ | 1811215276259147776 |
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| author | Jun Wang Jun Wang Xinrong Sun Lianying Jiao Zhengtao Xiao Farooq Riaz Yufeng Zhang Pengfei Xu Ruiqing Liu Tiantian Tang Meiqi Liu Dongmin Li |
| author_facet | Jun Wang Jun Wang Xinrong Sun Lianying Jiao Zhengtao Xiao Farooq Riaz Yufeng Zhang Pengfei Xu Ruiqing Liu Tiantian Tang Meiqi Liu Dongmin Li |
| author_sort | Jun Wang |
| collection | DOAJ |
| description | Objective: Our study aims to summarize and analyze the clinical characteristics of transient infantile hypertriglyceridemia (HTGTI) and variants in the glycerol-3-phosphate dehydrogenase 1 (GPD1) gene and the effect of HTGTI on the protein structure of GPD1.Methods: Retrospective analysis, using the general data, symptoms, signs, and auxiliary examinations, was performed on patients with HTGTI, which were confirmed by genetic testing in our hospital and reported cases online. The clinical data were analyzed using statistical and bioinformatic approaches.Results: A total of 31 genetically confirmed HTGTI patients were collected from our hospital and cases reported in the literature. The clinical manifestations showed the median age of onset was 6.0 (1.9, 12.0) months. All the patients had normal psychiatric status, but 22.6% of them presented growth retardation and short stature, 93.5% had hepatomegaly, and 16.1% had splenomegaly. Just a few children were reported with jaundice, cholestasis, and obesity (3.2–6.5%). The laboratory investigations showed that 96.8% of them had hypertriglyceridemia (HTG) with a median level of 3.1 (2.1, 5.5) mmol/L, but only 30.0% had returned to normal during follow-up. In addition, 93.5% of patients had elevated alanine aminotransferase (ALT) with an average level of 92.1 ± 43.5 U/L, while 38.7% had hypercholesterolemia. Upon abdominal imaging, all patients presented fatty liver and liver steatosis, with 66.7% of patients showing hepatic fibrosis. Statistical differences in triglyceride (TG) level were observed in the ≤6 months group compared with the older groups and in the 13 months to 6 years group with >6 years group (H = 22.02, P < 0.05). The restricted cubic spline model showed that severe HTG decreased in the early stage of infants to the normal level; however, it rebounded again to a mild or moderate level after the following days. The genetic test revealed that the main variant types of the GPD1 gene were missense variants (51.6%), followed by splicing variants (35.5%) and nonsense variants (12.9%). Of patients, 87.1% had homozygous variants, with the most frequent loci being c.361-1G > C and c.895G > A.Conclusion: The common manifestations of HTGTI were HTG, hepatomegaly, elevated liver transaminases, and hepatic steatosis in early infancy. However, the recurrence of aberrant HTG may pose long-term detrimental effects on HTGTI patients. |
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| spelling | doaj.art-0ca4fb85ad5a4892941b31ea3ce9c75c2022-12-22T03:44:21ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.916672916672Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 geneJun Wang0Jun Wang1Xinrong Sun2Lianying Jiao3Zhengtao Xiao4Farooq Riaz5Yufeng Zhang6Pengfei Xu7Ruiqing Liu8Tiantian Tang9Meiqi Liu10Dongmin Li11Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, ChinaSecond Department of Infectious Disease, Children’s Hospital Affiliated to Xi’an Jiaotong University, Xi’an, ChinaSecond Department of Infectious Disease, Children’s Hospital Affiliated to Xi’an Jiaotong University, Xi’an, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, ChinaCenter for Cancer Immunology Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, ChinaSecond Department of Infectious Disease, Children’s Hospital Affiliated to Xi’an Jiaotong University, Xi’an, ChinaSecond Department of Infectious Disease, Children’s Hospital Affiliated to Xi’an Jiaotong University, Xi’an, ChinaSecond Department of Infectious Disease, Children’s Hospital Affiliated to Xi’an Jiaotong University, Xi’an, ChinaSecond Department of Infectious Disease, Children’s Hospital Affiliated to Xi’an Jiaotong University, Xi’an, ChinaSecond Department of Infectious Disease, Children’s Hospital Affiliated to Xi’an Jiaotong University, Xi’an, ChinaDepartment of Biochemistry and Molecular Biology, School of Basic Medical Science, Xi’an Jiaotong University Health Science Center, Xi’an, ChinaObjective: Our study aims to summarize and analyze the clinical characteristics of transient infantile hypertriglyceridemia (HTGTI) and variants in the glycerol-3-phosphate dehydrogenase 1 (GPD1) gene and the effect of HTGTI on the protein structure of GPD1.Methods: Retrospective analysis, using the general data, symptoms, signs, and auxiliary examinations, was performed on patients with HTGTI, which were confirmed by genetic testing in our hospital and reported cases online. The clinical data were analyzed using statistical and bioinformatic approaches.Results: A total of 31 genetically confirmed HTGTI patients were collected from our hospital and cases reported in the literature. The clinical manifestations showed the median age of onset was 6.0 (1.9, 12.0) months. All the patients had normal psychiatric status, but 22.6% of them presented growth retardation and short stature, 93.5% had hepatomegaly, and 16.1% had splenomegaly. Just a few children were reported with jaundice, cholestasis, and obesity (3.2–6.5%). The laboratory investigations showed that 96.8% of them had hypertriglyceridemia (HTG) with a median level of 3.1 (2.1, 5.5) mmol/L, but only 30.0% had returned to normal during follow-up. In addition, 93.5% of patients had elevated alanine aminotransferase (ALT) with an average level of 92.1 ± 43.5 U/L, while 38.7% had hypercholesterolemia. Upon abdominal imaging, all patients presented fatty liver and liver steatosis, with 66.7% of patients showing hepatic fibrosis. Statistical differences in triglyceride (TG) level were observed in the ≤6 months group compared with the older groups and in the 13 months to 6 years group with >6 years group (H = 22.02, P < 0.05). The restricted cubic spline model showed that severe HTG decreased in the early stage of infants to the normal level; however, it rebounded again to a mild or moderate level after the following days. The genetic test revealed that the main variant types of the GPD1 gene were missense variants (51.6%), followed by splicing variants (35.5%) and nonsense variants (12.9%). Of patients, 87.1% had homozygous variants, with the most frequent loci being c.361-1G > C and c.895G > A.Conclusion: The common manifestations of HTGTI were HTG, hepatomegaly, elevated liver transaminases, and hepatic steatosis in early infancy. However, the recurrence of aberrant HTG may pose long-term detrimental effects on HTGTI patients.https://www.frontiersin.org/articles/10.3389/fgene.2022.916672/fullglycerol-3-phosphate dehydrogenase 1 (GPD1)transient infantile hypertriglyceridemia (HTGTI)hypertriglyceridemiahepatic steatosishepatomegaly |
| spellingShingle | Jun Wang Jun Wang Xinrong Sun Lianying Jiao Zhengtao Xiao Farooq Riaz Yufeng Zhang Pengfei Xu Ruiqing Liu Tiantian Tang Meiqi Liu Dongmin Li Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene Frontiers in Genetics glycerol-3-phosphate dehydrogenase 1 (GPD1) transient infantile hypertriglyceridemia (HTGTI) hypertriglyceridemia hepatic steatosis hepatomegaly |
| title | Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene |
| title_full | Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene |
| title_fullStr | Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene |
| title_full_unstemmed | Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene |
| title_short | Clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to GPD1 gene |
| title_sort | clinical characteristics and variant analyses of transient infantile hypertriglyceridemia related to gpd1 gene |
| topic | glycerol-3-phosphate dehydrogenase 1 (GPD1) transient infantile hypertriglyceridemia (HTGTI) hypertriglyceridemia hepatic steatosis hepatomegaly |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.916672/full |
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