Yap S, Rushe H, Howard P M, Naughten E R
National Center for Inherited Metabolic Disorders, The Children 's Hospital, Dublin, Ireland.
J Inherit Metab Dis. 2001 Aug;24(4):437-47. doi: 10.1023/a:1010525528842.
The pathological sequelae of untreated homocystinuria due to cystathionine beta-synthase deficiency include ectopia lentis, osteoporosis, thromboembolic events and mental retardation. They occur at a significantly higher rate with poorer mental capabilities (mean IQ = 57) in the untreated pyridoxine-nonresponsive individuals. The mental capabilities of 23 pyridoxine-nonresponsive individuals with 339 patient-years of treatment were assessed using age-appropriate psychometric tests and were compared to those of 10 unaffected siblings (controls). Of the 23 individuals, 19 were diagnosed through newborn screening with early treatment, two were late-detected and two were untreated at the time of assessment. Thirteen of the newborn, screened group who were compliant with treatment had no complications, while the remaining 6, who had poor compliance, developed complications. Good compliance was defined by a lifetime plasma free homocystine median < 11 micromol/L. The newborn screened, good compliance group (n = 13) with a mean age of 14.4 years (range 4.4-24.9) had mean full-scale IQ (FIQ) of 105.8 (range 84-120), while the poorly compliant group (n = 6) with a mean age of 19.9 years (range 13.8-25.5) had a mean FIQ of 80.8 (range 40-103). The control group (n = 10) with mean age of 19.4 years (range 9.7-32.9) years had a mean FIQ of 102 (range 76-116). The two late-detected patients aged 18.9 and 18.8 years had FIQ of 80 and 102, while the two untreated patients aged 22.4 and 11.7 years had FIQ of 52 and 53, respectively. There was no statistical evidence of significant differences between the compliant, early-treated individuals and their unaffected siblings (controls) except for the FIQ, which was significantly higher than that of the unaffected siblings (p = 0.0397). These data, despite the relatively small numbers, suggest that early treatment with good biochemical control (lifetime plasma free homocystine median < 11 micromol/L) seems to prevent mental retardation.
由于胱硫醚β-合酶缺乏导致的未经治疗的同型胱氨酸尿症的病理后遗症包括晶状体异位、骨质疏松、血栓栓塞事件和智力发育迟缓。在未经治疗的对吡哆醇无反应的个体中，这些后遗症的发生率显著更高，且智力水平较差（平均智商 = 57）。使用适合年龄的心理测量测试评估了23名对吡哆醇无反应的个体在339个患者年治疗期间的智力水平，并与10名未受影响的兄弟姐妹（对照组）进行了比较。在这23名个体中，19名通过新生儿筛查确诊并接受了早期治疗，2名发现较晚，2名在评估时未接受治疗。新生儿筛查组中13名依从治疗的患者没有并发症，而其余6名依从性差的患者出现了并发症。良好的依从性定义为终生血浆游离同型半胱氨酸中位数 < 11 μmol/L。新生儿筛查的良好依从性组（n = 13）平均年龄为14.4岁（范围4.4 - 24.9岁），平均全量表智商（FIQ）为105.8（范围84 - 120），而依从性差的组（n = 6）平均年龄为19.9岁（范围13.8 - 25.5岁），平均FIQ为80.8（范围40 - 103）。对照组（n = 10）平均年龄为19.4岁（范围9.7 - 32.9岁），平均FIQ为102（范围76 - 116）。两名发现较晚的患者年龄分别为18.9岁和18.8岁，FIQ分别为80和102，而两名未治疗的患者年龄分别为22.4岁和11.7岁，FIQ分别为52和53。除了FIQ显著高于未受影响的兄弟姐妹外（p = 0.0397），在依从治疗的早期治疗个体与其未受影响的兄弟姐妹（对照组）之间没有统计学证据表明存在显著差异。尽管数量相对较少，但这些数据表明早期治疗并实现良好的生化控制（终生血浆游离同型半胱氨酸中位数 < 11 μmol/L）似乎可以预防智力发育迟缓。
