GLYT1 encephalopathy is a form of glycine encephalopathy caused by disturbance of glycine transport. The phenotypic spectrum of the disease has not yet been completely described, as only four unrelated families with the disorder have been reported to date. Common features of affected patients include neonatal hypotonia, respiratory failure, encephalopathy, myoclonic jerks, dysmorphic features, and musculoeskeletal anomalies. All reported affected patients harbor biallelic genetic variants in SLC6A9. SNP array together with Sanger sequencing were performed in a newborn with arthrogryposis and severe neurological impairment. The novel genetic variant c.997delC in SLC6A9 was detected in homozygous state in the patient. At protein level, the predicted change is p.(Arg333Alafs*3), which most probably results in a loss of protein function. The variant cosegregated with the disease in the family. A subsequent pregnancy with ultrasound anomalies was also affected. The proband presented the core phenotypic features of GLYT1 encephalopathy, but also a burst suppression pattern on the electroencephalogram, a clinical feature not previously associated with the disorder. Our results suggest that the appearance of this pattern correlates with higher cerebrospinal fluid glycine levels and cerebrospinal fluid/plasma glycine ratios. A detailed discussion on the possible pathophysiological mechanisms of the disorder is also provided.

中文翻译：

---

GLYT1脑病：疾病表型的进一步描述和病理生理机制的讨论

GLYT1脑病是一种由甘氨酸转运障碍引起的甘氨酸脑病。该疾病的表型谱尚未完全描述，因为迄今为止仅报道了与该疾病无关的四个家族。受影响患者的常见特征包括新生儿肌张力减退，呼吸衰竭，脑病，肌阵挛性抽搐，畸形特征和肌肉骨骼异常。所有报告的患病患者在SLC6A9中都有双等位基因遗传变异。SNP阵列和Sanger测序在患有关节置换术和严重神经功能障碍的新生儿中进行。SLC6A9中的新型遗传变异体c.997delC在患者中以纯合子状态检测到。在蛋白质水平上，预测的变化是p。（Arg333Alafs * 3），这很可能导致蛋白质功能丧失。该变体与家庭中的疾病共隔离。随后的超声异常妊娠也受到影响。先证者表现出GLYT1脑病的核心表型特征，但在脑电图上也表现出爆发抑制模式，这是以前与该疾病无关的临床特征。我们的结果表明，这种模式的出现与较高的脑脊髓液甘氨酸水平和脑脊髓液/血浆甘氨酸比有关。还提供了对该疾病可能的病理生理机制的详细讨论。