经典的高半胱氨酸尿症是由于胱硫醚β-合酶(CBS)的缺乏,依赖吡哆醇的酶,取决于分子变体,可能是辅因子响应。升高的蛋氨酸通常被用作新生儿筛查(NBS)中检测CBS缺乏症(CBSD)的主要分析物,但是由于对其他临床意义不太明确的生化疾病的检测增加而受到限制,例如甲硫氨酸转氨酶(MAT)I/III杂合子。我们的州已经实现了CBSD的两层NBS算法,成功地减少了MATI/III杂合子的数量,然而有效地检测到了一种温和的,CBSD的辅因子响应形式。初步诊断后,患有CBSD的新生儿经常接受高剂量吡哆醇的吡哆醇攻击以确定反应性。在这里,我们描述了我们的NBS鉴定的患者,患有轻度形式的吡哆醇反应性CBSD,在吡哆醇攻击期间出现呼吸衰竭和横纹肌溶解,与吡哆醇毒性一致。该病例强调了新生儿对吡哆醇激发的基于体重的给药和持续时间建议的必要性。
Classic homocystinuria is due to deficiency of cystathionine beta-synthase (CBS), a pyridoxine-dependent enzyme that, depending on the molecular variants, may be co-factor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a two-tier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, co-factor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with high-dose pyridoxine to determine responsiveness. Here we describe our NBS-identified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weight-based dosing and duration recommendations for pyridoxine challenge in neonates.