Abstract：
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome is an extremely rare disorder of urea cycle, with few patients reported worldwide. Despite hyperammonemia control, the long-term outcome remains poor with progressive neurological deterioration. We report the clinical, biochemical, and molecular features of two Lebanese siblings diagnosed with this disorder and followed for 8 and 15 years, respectively. Variable clinical manifestations and neurological outcome were observed. The patient with earlier onset of symptoms had a severe neurological deterioration while the other developed a milder form of the disease at an older age. Diagnosis was challenging in the absence of the complete biochemical triad and the non-specific clinical presentations. Whole exome sequencing revealed a homozygous variant, p.Phe188del, in the SLC25A15 gene, a French- Canadian founder mutation previously unreported in Arab patients. Hyperammonemia was controlled in both patients but hyperonithinemia persisted. Frequent hyperalaninemia spikes and lactic acidosis occured concomitantly with the onset of seizures in one of the siblings. Variable neurological deterioration and outcome were observed within the same family. This is the first report from the Arab population of the long-term outcome of this devastating neurometabolic disorder.
摘要：
高鸟血-高氨血症-高瓜氨酸尿综合征是一种极为罕见的尿素循环障碍，在全球范围内报告的患者很少。尽管控制了高氨血症,进行性神经系统恶化的长期结局仍然很差.我们报告临床，生物化学，以及两名被诊断患有这种疾病的黎巴嫩兄弟姐妹的分子特征，并随访了8年和15年，分别。观察各种临床表现和神经系统转归。症状较早发作的患者神经系统严重恶化，而另一个患者在年龄较大时发展为较温和的疾病形式。在缺乏完整的生化三联征和非特异性临床表现的情况下，诊断具有挑战性。全外显子组测序揭示了一个纯合变体，p.Phe188del,在SLC25A15基因中，以前在阿拉伯患者中未报告的法国-加拿大创始人突变。两名患者的高氨血症均得到控制，但高钠血症持续存在。经常发生的高丙氨酸血症峰值和乳酸性酸中毒伴随着其中一个兄弟姐妹的癫痫发作。在同一家庭中观察到可变的神经系统恶化和结果。这是阿拉伯人口对这种毁灭性神经代谢紊乱的长期结果的第一份报告。
