Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, United States of America.
Baylor Scott & White Research Institute, Institute of Metabolic Disease, Dallas, TX, United States of America.
Mol Genet Metab. 2019 Sep-Oct;128(1-2):109-112. doi: 10.1016/j.ymgme.2019.07.010. Epub 2019 Jul 18.
Increased gamma-hydroxybutyric acid in urine and blood are metabolic hallmarks of succinic semialdehyde dehydrogenase deficiency, a defect of 4-aminobutyric acid metabolism. Here, we examined the hypothesis that succinic semialdehyde dehydrogenase deficiency could be identified via measurement of gamma-hydroxybutyric acid in newborn and post-newborn dried bloodspots. Quantitation of gamma-hydroxybutyric acid using liquid chromatography-tandem mass spectrometry in twelve archival newborn patient dried bloodspots was 360 ± 57 μM (mean, standard error; range 111-767), all values exceeding the previously established cutoff for newborn detection of 78 μΜ established from 2831 dried bloodspots derived from newborns, neonates and children. Gamma-hydroxybutyric acid in post-newborn dried bloodspots (n = 19; ages 0.8-38 years) was 191 ± 65 μM (mean, standard error; range 20-1218), exceeding the aforementioned GHB cutoff for patients approximately 10 years of age or younger. Further, gamma-hydroxybutyric acid in post-newborn dried bloodspots displayed a significant (p < .0001) inverse correlation with age. This preliminary study suggests that succinic semialdehyde dehydrogenase deficiency may be identified in newborn and post-newborn dried bloodspots via quantitation of gamma-hydroxybutyric acid, while forming the platform for more extensive studies in affected and unaffected dried bloodspots.
尿液和血液中γ-羟基丁酸含量增加是琥珀酸半醛脱氢酶缺乏症的代谢特征，这是一种 4-氨基丁酸代谢缺陷。在此，我们通过检测新生儿和新生儿后干血斑中γ-羟基丁酸的含量来检验琥珀酸半醛脱氢酶缺乏症的假设。使用液相色谱-串联质谱法在 12 个存档的新生儿患者干血斑中定量γ-羟基丁酸，其含量为 360±57µM（平均值，标准误差；范围 111-767），所有值均超过先前建立的 78µM 新生儿检测界值，该界值是从 2831 个源自新生儿、婴儿和儿童的干血斑中确定的。新生儿后干血斑（n=19；年龄 0.8-38 岁）中的γ-羟基丁酸为 191±65µM（平均值，标准误差；范围 20-1218），超过了上述针对 10 岁或更小患者的 GHB 界值。此外，新生儿后干血斑中的γ-羟基丁酸与年龄呈显著（p<0.0001）负相关。这项初步研究表明，琥珀酸半醛脱氢酶缺乏症可能通过定量γ-羟基丁酸在新生儿和新生儿后干血斑中被识别，同时为在受影响和未受影响的干血斑中进行更广泛的研究奠定了基础。
