title: Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family.
abstract: 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.
authors.affiliation: Department of Neurology, University Hospital of Leiden, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Vermeij
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: O J
authors.initials: OJ
authors.lastname: Buruma
authors.forename: H
authors.initials: H
authors.lastname: Veenema
authors.forename: F A
authors.initials: FA
authors.lastname: de Wolff
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010375:Pedigree; D010672:Phenytoin / Q000097:blood / Q000378:metabolism*
chemical_list: D010672:Phenytoin