Huang Yue, Sharma Rajesh, Feigenbaum Annette, Lee Chung, Sahai Inderneel, Sanchez Russo Rossana, Neira Juanita, Brooks Susan Sklower, Jackson Kelly E, Wong Derek, Cederbaum Stephen, Lacbawan Felicitas L, Rowland Charles M, Tanpaiboon Pranoot, Salazar Denise
Division of Medical Genetics, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, United States of America.
Biochemical Genetics, Advanced Diagnostics-Genetics, Genomics and R&D, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, United States of America.
Mol Genet Metab Rep. 2021 Mar 3;27:100735. doi: 10.1016/j.ymgmr.2021.100735. eCollection 2021 Jun.
Arginase deficiency is a rare inborn error of metabolism that interrupts the final step of the urea cycle. Untreated individuals often present with episodic hyperammonemia, developmental delay, cognitive impairment, and spasticity in early childhood. The newborn screening (NBS) algorithms for arginase deficiency vary between individual states in the US but often include hyperargininemia and elevated arginine to ornithine (Arg/Orn) ratio. Here, we report 14 arginase deficiency cases, including two patients with positive NBS for hyperargininemia in whom the diagnosis of arginase deficiency was delayed owing to normal or near normal plasma arginine levels on follow-up testing. To improve the detection capability for arginase deficiency, we evaluated plasma Arg/Orn ratio as a secondary diagnostic marker in positive NBS cases for hyperargininemia. We found that plasma Arg/Orn ratio combined with plasma arginine was a better marker than plasma arginine alone to differentiate patients with arginase deficiency from unaffected newborns. In fact, elevated plasma arginine in combination with an Arg/Orn ratio of ≥1.4 identified all 14 arginase deficiency cases. In addition, we examined the impact of age on plasma arginine and ornithine levels. Plasma arginine increased 0.94 μmol/L/day while ornithine was essentially unchanged in the first 31 days of life, which resulted in a similar increasing trend for the Arg/Orn ratio (0.01/day). This study demonstrated that plasma Arg/Orn ratio as a secondary diagnostic marker improved the detection capability for arginase deficiency in newborns with hyperargininemia, which will allow timely detection of arginase deficiency and hence initiation of treatment before developing symptoms.
精氨酸酶缺乏症是一种罕见的先天性代谢缺陷，它会干扰尿素循环的最后一步。未经治疗的个体在幼儿期常出现发作性高氨血症、发育迟缓、认知障碍和痉挛。美国各州针对精氨酸酶缺乏症的新生儿筛查（NBS）算法各不相同，但通常包括高精氨酸血症以及精氨酸与鸟氨酸（Arg/Orn）比值升高。在此，我们报告了14例精氨酸酶缺乏症病例，其中包括2例高精氨酸血症新生儿筛查呈阳性的患者，其精氨酸酶缺乏症的诊断因后续检测时血浆精氨酸水平正常或接近正常而延迟。为提高对精氨酸酶缺乏症的检测能力，我们评估了血浆Arg/Orn比值作为高精氨酸血症新生儿筛查阳性病例的辅助诊断标志物。我们发现，与单独的血浆精氨酸相比，血浆Arg/Orn比值结合血浆精氨酸是区分精氨酸酶缺乏症患者与未受影响新生儿的更好标志物。事实上，血浆精氨酸升高且Arg/Orn比值≥1.4可识别出所有14例精氨酸酶缺乏症病例。此外，我们研究了年龄对血浆精氨酸和鸟氨酸水平的影响。在生命的前31天，血浆精氨酸每天增加0.94 μmol/L，而鸟氨酸基本不变，这导致Arg/Orn比值出现类似的上升趋势（每天0.01）。本研究表明，血浆Arg/Orn比值作为辅助诊断标志物可提高对高精氨酸血症新生儿精氨酸酶缺乏症的检测能力，这将有助于及时检测出精氨酸酶缺乏症，从而在出现症状之前开始治疗。
