Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family

The mode of inheritance of insufficient phenytoin p-hydroxylation was studied in the family of a patient who had previously suffered from a phenytoin intoxication caused by insufficient metabolism of this drug. This family was compared with a control group. The rate of phenytoin metabolism was derived from the phenytoin/metabolite ratio in serum 6 hours after an oral test dose of 300 mg phenytoin. The propositus, a brother and a sister, were very slow metabolizers of phenytoin, with a metabolic ratio of approximately 20. In the other individuals, 22 family members of the second generation and 37 control subjects, a metabolic ratio of 4.7 +/- 2.2 (mean +/- SD; n = 59) was found. When comparing the members of the second generation (F2) with the control group, two statistically significantly different groups appear to exist: F2, with a metabolic ratio of 6.6 +/- 1.7 (mean +/- SD; n = 22), and the control group, with a metabolic ratio of 3.7 +/- 1.8 (mean +/- SD; n = 37) (p less than 0.001). Based on these results the mode of inheritance of this defect seems to be autosomal recessive.