Ernst M, Zametkin A J, Matochik J A, Pascualvaca D, Jons P H, Hardy K, Hankerson J G, Doudet D J, Cohen R M
Laboratory of Cerebral Metabolism, National Institute of Mental Health, Bethesda, MD 20892-4030, USA.
N Engl J Med. 1996 Jun 13;334(24):1568-72. doi: 10.1056/NEJM199606133342403.
Lesch-Nyhan disease is a rare, devastating, X-linked recessive disorder of purine synthesis. Patients present with hyperuricemia, choreoathetosis, dystonia, and aggressive and self-injurious behavior. Although the genetic and biochemical abnormalities have been identified, the causes of the neuropsychiatric syndrome remain unclear.
We used positron-emission tomography to measure presynaptic accumulation of fluorodopa F 18 tracer in the dopaminergic regions of the brains of 12 patients with Lesch-Nyhan disease (age, 10 to 20 years) and 15 healthy controls (age, 12 to 23). The results were expressed as ratios of specific to nonspecific radioactive counts. A low ratio indicates decreased dopa decarboxylase activity and dopamine storage.
The fluorodopa F 18 ratio was significantly lower in the putamen (31 percent of control values), caudate nucleus (39 percent), frontal cortex (44 percent), and ventral tegmental complex (substantia nigra and ventral tegmentum; 57 percent) in the patients with Lesch-Nyhan disease than in the controls. Uptake of the tracer was abnormally low even in the youngest patients tested, and there was no overlap in the values between patients and controls.
Patients with Lesch-Nyhan disease have abnormally few dopaminergic nerve terminals and cell bodies. The abnormality involves all dopaminergic pathways and is not restricted to the basal ganglia. These dopaminergic deficits are pervasive and appear to be developmental in origin, which suggests that they contribute to the characteristic neuropsychiatric manifestations of the disease.
莱施-奈恩病是一种罕见的、严重的、X连锁隐性嘌呤合成障碍疾病。患者表现为高尿酸血症、舞蹈手足徐动症、肌张力障碍以及攻击和自伤行为。尽管已经明确了其遗传和生化异常，但神经精神综合征的病因仍不清楚。
我们使用正电子发射断层扫描来测量12例莱施-奈恩病患者（年龄10至20岁）和15名健康对照者（年龄12至23岁）大脑多巴胺能区域中氟多巴F 18示踪剂的突触前积聚情况。结果以特异性与非特异性放射性计数的比值表示。比值低表明多巴脱羧酶活性和多巴胺储存减少。
莱施-奈恩病患者壳核（对照值的31%）、尾状核（39%）、额叶皮质（44%）和腹侧被盖复合体（黑质和腹侧被盖区；57%）的氟多巴F 18比值显著低于对照组。即使在最年轻的受试患者中，示踪剂摄取也异常低，患者和对照组的值没有重叠。
莱施-奈恩病患者的多巴胺能神经末梢和细胞体异常少。这种异常涉及所有多巴胺能通路，并不局限于基底神经节。这些多巴胺能缺陷普遍存在，似乎起源于发育过程，这表明它们导致了该疾病典型的神经精神表现。
