Section of Pediatrics, Department of Translational Medicine, University of Naples "Federico II", Naples, Italy; Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy; CEINGE Biotecnologie Avanzate s.c.ar.l., Naples, Italy.
J Lipid Res. 2024 Oct;65(10):100651. doi: 10.1016/j.jlr.2024.100651. Epub 2024 Sep 19.
Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls. Metabolic control and dietary information biochemical markers were obtained from patients with GSDIa. Patients with GSDIa showed higher total serum lysophosphatidylcholine (Fold Change, (FC) 2.2, P < 0.0001), acyl-acyl-phosphatidylcholine (FC 2.1, P < 0.0001), and ceramide (FC 2.4, P < 0.0001) levels and bile acid (FC 0.7, P < 0.001), acylcarnitines (FC 0.7, P < 0.001), and cholesterol esters (FC 1.0, P < 0.001) than those of healthy controls, and higher di- (FC 1.1, P < 0.0001; FC 0.9, P < 0.01) and triacylglycerol (FC 6.3, P < 0.0001; FC 3.9, P < 0.01) levels than those of healthy controls and hypercholesterolemic subjects. Both total cholesterol and triglyceride values correlated with Cer (d16:1/22:0), Cer (d18:1/20:0), Cer (d18:1/20:0(OH)), Cer (d18:1/22:0), Cer (d18:1/23:0), Cer (d18:1/24:1), Cer (d18:2/22:0), Cer (d18:2/24:1). Total cholesterol also correlated with Cer (d18:1/24:0), Cer (d18:2/20:0), HexCer (d16:1/22:0), HexCer (d18:1/18:0), and Hex2Cer (d18:1/20:0). Triglyceridelevels correlated with Cer (d18:0/24:1). Alanine aminotransferase values correlated with Cer (d18:0/22:0), insulin with Cer (d18:1/22:1) and Cer (d18:1/24:1), and HDL with hexosylceramide (HexCer) (d18:2/23:0). These results expand on the currently known involvement of lipid metabolism in GSDIa. Circulating Cer may allow for refined dietary assessment compared with traditional biomarkers. Because specific lipid species are relatively easy to assess, they represent potential novel biomarkers of GSDIa.
糖原贮积病 Ia 型（GSDIa）是一种罕见的遗传性葡萄糖-6-磷酸酶-α（G6Pase-α）缺乏引起的碳水化合物代谢紊乱。尽管高脂血症是 GSDI 的标志之一，但脂质代谢紊乱的程度仍不完全清楚。通过包括年龄和性别匹配的健康对照组和年龄匹配的高胆固醇对照组，进行脂质组学分析以描述 GSDIa 患者的血清脂质组。从 GSDIa 患者中获得代谢控制和饮食信息生化标志物。GSDIa 患者的总血清溶血磷脂酰胆碱（FC 2.2，P<0.0001）、酰基-酰基磷脂酰胆碱（FC 2.1，P<0.0001）和神经酰胺（FC 2.4，P<0.0001）水平以及胆汁酸（FC 0.7，P<0.001）、酰基肉碱（FC 0.7，P<0.001）和胆固醇酯（FC 1.0，P<0.001）水平均高于健康对照组，二酰基甘油（FC 1.1，P<0.0001；FC 0.9，P<0.01）和三酰基甘油（FC 6.3，P<0.0001；FC 3.9，P<0.01）水平均高于健康对照组和高胆固醇对照组。总胆固醇和甘油三酯值与 Cer（d16:1/22:0）、Cer（d18:1/20:0）、Cer（d18:1/20:0（OH））、Cer（d18:1/22:0）、Cer（d18:1/23:0）、Cer（d18:1/24:1）、Cer（d18:2/22:0）和 Cer（d18:2/24:1）相关。总胆固醇还与 Cer（d18:1/24:0）、Cer（d18:2/20:0）、HexCer（d16:1/22:0）、HexCer（d18:1/18:0）和 Hex2Cer（d18:1/20:0）相关。甘油三酯水平与 Cer（d18:0/24:1）相关。丙氨酸氨基转移酶值与 Cer（d18:0/22:0）、胰岛素与 Cer（d18:1/22:1）和 Cer（d18:1/24:1）以及高密度脂蛋白与己糖神经酰胺（HexCer）（d18:2/23:0）相关。这些结果扩展了目前已知的脂质代谢在 GSDIa 中的参与。与传统生物标志物相比，循环神经酰胺可能允许更精细的饮食评估。由于特定的脂质种类相对容易评估，因此它们代表 GSDIa 的潜在新型生物标志物。
