Abstract：
BACKGROUND: Elevated 3-hydroxyisovaleryl-/2-methyl-3-hydroxybutyryl (C5-OH) acylcarnitine in blood can result from several genetic enzyme deficiencies: 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy 3-methylglutaryl-CoA lyase deficiency, beta-ketothiolase deficiency, 2-methyl 3-hydroxybutyryl-CoA dehydrogenase deficiency, primary 3-methylglutaconic aciduria, multiple biotin-dependent carboxylase deficiencies and biotin metabolism disorders. Biochemical tests help differentiate these causes while molecular tests are usually required for definitive diagnosis.
METHODS: We reported an infant girl with newborn screen findings of elevated C5-OH acylcarnitine. She had further confirmational biochemical testing including plasma acylcarnitines, urine organic acids and urine acylglycines. Patient\'s urine organic acid profile showed markedly increased 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. Urine acylglycine test reported a large increase of 3-methylcrotonylglycine and plasma acylcarnitine test repeated the finding of elevated C5-OH acylcarnitine together with propionyl acylcarnitine elevation. These results point to multiple biotin-dependent carboxylase deficiency. Molecular tests revealed a homozygous mutation in the holocarboxylase synthetase gene that is consistent with her biochemical test findings. This case demonstrated the critical role of newborn screen in identifying inborn errors of metabolism that may otherwise be missed and lead to severe morbidity later in life. It also showcased that both biochemical and molecular tests are essential tools in the diagnosis.
METHODS: We reported an infant girl with newborn screen findings of elevated C5-OH acylcarnitine. She had further confirmational biochemical testing including plasma acylcarnitines, urine organic acids and urine acylglycines. Patient\'s urine organic acid profile showed markedly increased 3-hydroxyisovaleric acid and 3-methylcrotonylglycine. Urine acylglycine test reported a large increase of 3-methylcrotonylglycine and plasma acylcarnitine test repeated the finding of elevated C5-OH acylcarnitine together with propionyl acylcarnitine elevation. These results point to multiple biotin-dependent carboxylase deficiency. Molecular tests revealed a homozygous mutation in the holocarboxylase synthetase gene that is consistent with her biochemical test findings. This case demonstrated the critical role of newborn screen in identifying inborn errors of metabolism that may otherwise be missed and lead to severe morbidity later in life. It also showcased that both biochemical and molecular tests are essential tools in the diagnosis.
摘要：
背景：血液中3-羟基异戊酰基-/2-甲基-3-羟基丁酰基（C5-OH）酰基肉碱的升高可由几种遗传酶缺陷引起：3-甲基巴豆酰辅酶A羧化酶缺乏症，3-羟基3-甲基戊二酰辅酶A裂解酶缺乏症，β-酮硫解酶缺乏症，2-甲基3-羟基丁酰辅酶A脱氢酶缺乏症，原发性3-甲基戊二酸尿症，多种生物素依赖性羧化酶缺乏和生物素代谢紊乱。生化测试有助于区分这些原因，而分子测试通常需要明确的诊断。
方法：我们报道了一名新生儿筛查中C5-OH酰基肉碱升高的女婴。她进行了进一步的确认生化测试，包括血浆酰基肉碱，尿有机酸和尿酰基甘氨酸。患者的尿有机酸谱显示3-羟基异戊酸和3-甲基巴豆基甘氨酸显著增加。尿液酰基甘氨酸测试报告了3-甲基巴豆酰基甘氨酸的大量增加，血浆酰基肉碱测试重复了C5-OH酰基肉碱升高和丙酰基酰基肉碱升高的发现。这些结果指出了多种生物素依赖性羧化酶缺陷。分子测试显示全羧化酶合成酶基因中的纯合突变与她的生化测试结果一致。此病例证明了新生儿筛查在识别先天性代谢错误中的关键作用，否则可能会被错过并导致以后的严重发病率。它还表明，生化和分子测试是诊断中必不可少的工具。
方法：我们报道了一名新生儿筛查中C5-OH酰基肉碱升高的女婴。她进行了进一步的确认生化测试，包括血浆酰基肉碱，尿有机酸和尿酰基甘氨酸。患者的尿有机酸谱显示3-羟基异戊酸和3-甲基巴豆基甘氨酸显著增加。尿液酰基甘氨酸测试报告了3-甲基巴豆酰基甘氨酸的大量增加，血浆酰基肉碱测试重复了C5-OH酰基肉碱升高和丙酰基酰基肉碱升高的发现。这些结果指出了多种生物素依赖性羧化酶缺陷。分子测试显示全羧化酶合成酶基因中的纯合突变与她的生化测试结果一致。此病例证明了新生儿筛查在识别先天性代谢错误中的关键作用，否则可能会被错过并导致以后的严重发病率。它还表明，生化和分子测试是诊断中必不可少的工具。
