Classical homocystinuria (HCU) is a genetic disorder caused by mutations in the cystathionine beta synthase gene, which results in impaired metabolism of the sulfur-bearing amino acid homocysteine and its accumulation in blood and tissues. Classical HCU can be detected via newborn screening in the United States, but the test is widely acknowledged to miss many patients. While severely elevated homocysteine levels (>100 μmol /L) frequently lead to a classical HCU diagnosis, intermediate levels (>30 to 100 μmol /L), though linked to many of the known complications of HCU, are not always recognized as associated with HCU. We aimed to identify and describe potentially undiagnosed classical HCU patients using a nationally-representative database of administrative claims and laboratory results. We estimated the national prevalence of patients with homocysteine >30 μmol /L, and compared their demographic and clinical characteristics to those of patients with homocysteine levels ≤30 μmol/L. Among 57,580 patients with a homocysteine test result, 1.8% had a value >30 μmol /L. Patients with homocysteine >30 μmol /L were more frequently diagnosed with hypothyroidism (39.2% vs. 20.7%, p < .001) and renal disease (9.7% vs. 5.5%, p < .001), and were more likely to have a prescription for an anxiolytic/antidepressant (44.5% vs. 38.9%), opioid (58.4% vs. 53.1%), steroid (46.4% vs. 42.5%), or thyroid hormone (38.8% vs. 18.8%), compared to patients with homocysteine ≤30 μmol /L (all p < .05). Both groups were equally likely to have a diagnosis of homocystinuria or another disorder of sulfur-bearing amino acid metabolism (3.8% vs. 4.0%, p = .752). The age-adjusted national prevalence of homocysteine >30 μmol /L was estimated at 33,068 (95% CI: 1033 - 35,104). These findings suggest that thousands of people in the US may be living with intermediate to severely elevated homocysteine levels and may require further evaluation for the presence of classical HCU.

中文翻译：

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美国中度至严重升高的总同型半胱氨酸水平的估计患病率：错过了诊断同型半胱氨酸尿症的机会吗？

经典高半胱氨酸尿症（HCU）是由胱硫醚β合酶基因突变引起的遗传性疾病，其导致含硫氨基酸高半胱氨酸的代谢受损及其在血液和组织中的积累。在美国，可以通过新生儿筛查来检测经典HCU，但该方法被广泛认为遗漏了许多患者。尽管同型半胱氨酸水平严重升高（> 100μmol/ L）经常会导致经典的HCU诊断，但中间水平（> 30至100μmol/ L）尽管与许多已知的HCU并发症有关，但并不总是被认为与HCU。我们旨在使用国家代表的行政声明和实验室结果数据库来识别和描述可能未被诊断的经典HCU患者。我们估算了高半胱氨酸> 30μmol/ L的全国患病率，并将其人口统计学和临床​​特征与高半胱氨酸水平≤30μmol/ L的患者进行了比较。在有高半胱氨酸测试结果的57580名患者中，有1.8％的值> 30μmol/ L。同型半胱氨酸> 30μmol/ L的患者更常被诊断为甲状腺功能减退（39.2％vs. 20.7％，p <.001）和肾病（9.7％vs. 5.5％，p <.001），并且更有可能患有与抗焦虑药/抗抑郁药（44.5％比38.9％），阿片类药物（58.4％比53.1％），类固醇（46.4％比42.5％）或甲状腺激素（38.8％比18.8％）的处方相比同型半胱氨酸≤30μmol/ L的患者（均p <.05）。两组均被诊断为同型半胱氨酸尿症或另一种含硫氨基酸代谢异常（3.8％vs.4）。0％，p = .752）。经年龄调整的高半胱氨酸> 30μmol/ L的全国患病率估计为33,068（95％CI：1033-35,104）。这些发现表明，美国成千上万的人可能正处于同型半胱氨酸水平或严重升高的水平，并且可能需要进一步评估经典HCU的存在。