Hyperphosphatasia with neurologic deficit: a pyridoxine-responsive seizure disorder?

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism*
  • Child, Preschool
  • Developmental Disabilities / enzymology
  • Developmental Disabilities / etiology
  • Epilepsy, Tonic-Clonic / drug therapy*
  • Epilepsy, Tonic-Clonic / enzymology
  • Epilepsy, Tonic-Clonic / etiology
  • Female
  • Humans
  • Infant
  • Metal Metabolism, Inborn Errors / complications*
  • Metal Metabolism, Inborn Errors / enzymology
  • Metal Metabolism, Inborn Errors / psychology
  • Pyridoxine / therapeutic use*
  • Vitamin B Complex / therapeutic use*


  • Vitamin B Complex
  • Alkaline Phosphatase
  • Pyridoxine