Thompson Miles D, Killoran Annie, Percy Maire E, Nezarati Marjan, Cole David E C, Hwang Paul A
Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
Pediatr Neurol. 2006 Apr;34(4):303-7. doi: 10.1016/j.pediatrneurol.2005.08.020.
This report describes the case of a 4 1/2-year-old female with developmental delay and tonic-clonic seizures, persistently elevated serum alkaline phosphatase activity, and low serum pyridoxal 5'-phosphate. Born at term to consanguineous parents, she was dysmorphic and delayed at 5 months. At 11 months, seizures and microcephaly were evident but skeletal and cerebral imaging, karyotyping, and genetic metabolic tests were unremarkable. Serum alkaline phosphatase activity, however, was elevated (1.3 +/- 0.6 times greater than the upper limit of normal) on seven occasions between 5 months and 4(1/2) years of age. Hyperphosphatasia with neurologic deficit (MIM #239300), a rare autosomal recessive disorder, was diagnosed. The low serum levels of pyridoxal 5'-phosphate (6 nmol/L; normal >20 nmol/L) prompted a pyridoxine challenge. A clinically significant but paradoxical response was observed. On electroencephalography, diffuse delta slow waves (1-2 Hz) were observed, suggestive of stage 3 or 4 slow-wave sleep. With daily administration of 100 mg pyridoxine and withdrawal of phenobarbital, seizures were not evident. We suggest that serum alkaline phosphatase should be measured in cases of seizures with paradoxical electroencephalographic response to pyridoxine. Conversely, pyridoxine challenge should be considered in cases of hyperphosphatasia with seizures and neurologic deficit.
本报告描述了一名4岁半女性病例，该患者有发育迟缓及强直阵挛性癫痫发作，血清碱性磷酸酶活性持续升高，血清5'-磷酸吡哆醛水平较低。她足月出生，父母为近亲结婚，5个月时出现发育异常及发育迟缓。11个月时，癫痫发作及小头畸形明显，但骨骼及脑部影像学检查、染色体核型分析及遗传代谢检查均无异常。然而，在5个月至4岁半期间，血清碱性磷酸酶活性有7次升高（比正常上限高1.3±0.6倍）。诊断为伴有神经功能缺损的高磷酸酶血症（MIM #239300），这是一种罕见的常染色体隐性疾病。血清5'-磷酸吡哆醛水平较低（6 nmol/L；正常>20 nmol/L）促使进行吡哆醇激发试验。观察到一种临床上显著但矛盾的反应。脑电图显示弥漫性δ慢波（1 - 2 Hz），提示处于3期或4期慢波睡眠。每日给予100 mg吡哆醇并停用苯巴比妥后，癫痫发作未再出现。我们建议，对于对吡哆醇有矛盾脑电图反应的癫痫病例，应检测血清碱性磷酸酶。相反，对于伴有癫痫发作及神经功能缺损的高磷酸酶血症病例，应考虑进行吡哆醇激发试验。
