The Proline/Citrulline Ratio as a Biomarker for OAT Deficiency in Early Infancy
The Proline/Citrulline Ratio as a Biomarker for OAT Deficiency in Early Infancy
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DOI：
10.1007/8904_2011_122
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
van Hasselt, Peter
中科院分区：
文献类型：
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作者：
de Sain-van der Velden, Monique G. M.;Rinaldo, Piero;van Hasselt, Peter
人类鸟氨酸-德尔塔-氨基转移酶(OAT)缺乏会导致脑回萎缩。早期诊断可以在不可逆转的损害发生之前开始治疗。然而，由于最初症状的非特异性，诊断通常被推迟到成年。在这里，我们报告了一例新生儿的研究结果，该新生儿因有燕麦缺乏的阳性家族史而接受评估。在婴儿早期，反转的酶流通量导致临界低鸟氨酸浓度--引起尿素循环紊乱--和增加的脯氨酸。此外，血浆瓜氨酸水平较低。因此，与对照组相比，血浆中的脯氨酸/瓜氨酸比值升高。为了找出新生儿干血斑点中的氨基酸图谱是否适合于检测燕麦缺乏，我们评估了两名受影响患者的原始新生儿干血斑点，并将其与2004年以来在明尼苏达州测试的45万名新生儿的数据库进行了比较。脯氨酸浓度(777mU/L和1381mU/L)高于一般人群99个百分位数(776mU/L)，瓜氨酸浓度(4.5mU/L和4.9mU/L)仅略高于1%(4.37mU/L)。脯氨酸/瓜氨酸比值分别为172.9和281.8。这一比率是在正常人群中回溯计算的，99%是97.6。将这一比率应用于NBS可以导致早期和特异性地检测新生儿燕麦缺乏，而不需要新生儿筛查实验室量化氨基酸的额外费用。鉴于燕麦病的早期诊断可以导致更早的治疗和预防视力损害，建议进行进一步的研究，以评估是否有必要对新生儿进行燕麦缺乏筛查。
Deficiency of ornithine-delta-aminotransferase (OAT) in humans results in gyrate atrophy. Early diagnosis may allow initiation of treatment before irreversible damage has occurred. However, diagnosis is commonly delayed well into adulthood because of the nonspecific character of initial symptoms. Here, we report findings in a neonate who was evaluated because of a positive family history of OAT deficiency. The reversed enzymatic flux in early infancy resulted in borderline low ornithine concentration - evoking urea cycle disturbances - and increased proline. In addition, plasma citrulline was low. Consequently, the proline/citrulline ratio in plasma was increased compared to controls. To find out whether amino acid profiling in neonatal dried blood spots is suitable to detect OAT deficiency, we evaluated the original newborn dried blood spots of two affected patients and compared it with a database of >450,000 newborns tested in Minnesota since 2004. Proline concentrations (777 and 1,381 mu mol/L) were above the 99 percentile (776 mu mol/L) of the general population, and citrulline concentrations (4.5 and 4.9 mu mol/L) only just above the 1 percentile (4.37 mu mol/L). The proline/citrulline ratio was 172.9 and 281.8, respectively. This ratio was calculated retrospectively in the normal population, and the 99 percentile was 97.6. Applying this ratio for NBS could lead to early and specific detection of neonatal OAT deficiency, with no additional expense to newborn screening laboratories quantifying amino acids. Given that early diagnosis of OAT disease can lead to earlier treatment and prevent visual impairment, further studies are indicated to evaluate whether newborn screening for OAT deficiency is warranted.