Gariani Karim, Klauser Antoine, Vargas Maria Isabel, Lazeyras François, Tran Christel
Division of Endocrinology, Diabetes, Hypertension and Therapeutic Patient Education, Geneva University Hospitals, University of Geneva, 1205 Geneva, Switzerland.
Department of Radiology and Medical Informatics, University of Geneva, 1211 Geneva, Switzerland.
Brain Sci. 2022 Mar 15;12(3):389. doi: 10.3390/brainsci12030389.
Hyperinsulinism/hyperammonemia syndrome (HI/HA) is an autosomal dominant disorder caused by monoallelic activating mutations in the glutamate dehydrogenase 1 () gene. While hyperinsulinism may be explained by a reduction in the allosteric inhibition of , the pathogenesis of HA in HI/HA remains uncertain; interestingly, HA in the HI/HA syndrome is not associated with acute hyperammonemic intoxication events. We obtained a brain magnetic resonance (MR) in a woman with HI/HA syndrome with chronic asymptomatic HA. On MR spectroscopy, choline and myoinositol were decreased as in other HA disorders. In contrast, distinct from other HA disorders, combined glutamate and glutamine levels were normal (not increased). This observation suggests that brain biochemistry in HI/HA may differ from that of other HA disorders. In HI/HA, ammonia overproduction may come to the expense of glutamate levels, and this seems to prevent the condensation of ammonia with glutamate to produce glutamine that is typical of the other HA disorders. The absence of combined glutamate and glutamine elevation might be correlated to the absence of acute cerebral ammonia toxicity.
高胰岛素血症/高氨血症综合征（HI/HA）是一种常染色体显性疾病，由谷氨酸脱氢酶1（GDH1）基因的单等位基因激活突变引起。虽然高胰岛素血症可能是由于对GDH1变构抑制作用的降低所导致，但HI/HA中高氨血症的发病机制仍不明确；有趣的是，HI/HA综合征中的高氨血症与急性高氨血症中毒事件无关。我们对一名患有HI/HA综合征且伴有慢性无症状高氨血症的女性进行了脑部磁共振成像（MR）检查。在磁共振波谱分析中，胆碱和肌醇水平与其他高氨血症疾病一样降低。相比之下，与其他高氨血症疾病不同的是，谷氨酸和谷氨酰胺的联合水平正常（未升高）。这一观察结果表明，HI/HA中的脑生化情况可能与其他高氨血症疾病不同。在HI/HA中，氨的过量产生可能是以谷氨酸水平为代价的，这似乎阻止了氨与谷氨酸缩合生成其他高氨血症疾病中典型的谷氨酰胺。谷氨酸和谷氨酰胺联合水平未升高可能与急性脑氨毒性的缺乏有关。
