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Epilepsy in Phenylketonuria: A Complex Dependence on Serum Phenylalanine Levels
Author(s) -
Martynyuk Anatoly E.,
Ucar Deniz A.,
Yang Dawn D.,
Norman Wendy M.,
Carney Paul R.,
Dennis Donn M.,
Laipis Philip J.
Publication year - 2007
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2007.01115.x
Subject(s) - endocrinology , medicine , phenylalanine , epilepsy , evening , morning , phenylketonurias , hyperphenylalaninemia , phenylalanine hydroxylase , chemistry , amino acid , biochemistry , psychiatry , physics , astronomy
Summary: Purpose: Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism that frequently results in epilepsy if a low Phe diet was not implemented at birth. The mechanisms by which Phe affects the brain are poorly understood. Methods: Audiogenic seizures (AGS) were studied in female homozygous Pah enu2 BTBR (PKU) mice. Results: Adult PKU mice, 18–20 weeks of age, in contrast to wild‐type and heterozygous counterparts, exhibited a full range of AGS. Younger PKU mice, 5–7 weeks of age, had higher serum Phe levels (2.22 ± 0.20 mM) in comparison with the adult animals (1.72 ± 0.05 mM) and were not susceptible to AGS. Among adult mice, animals susceptible to AGS had significantly lower serum Phe levels (1.62 ± 0.06 mM) in comparison with those resistant to AGS (1.86 ± 0.07 mM). Susceptibility to AGS tended to increase in the afternoon when serum Phe concentration decreased in comparison to evening and morning. Normalization of serum Phe level by instituting a low Phe diet generally prevented susceptibility to AGS within 12 h. Although return to a standard diet raised Phe levels to hyperphenylalaninemic within 12 h in animals treated with a low Phe diet for 2 weeks, more than 7 weeks were needed for a complete resumption of AGS. Conclusions: Transient decrease in Phe levels within hyperphenylalaninemic range may be a necessary condition for PKU‐related seizures to occur. A low Phe diet prevents susceptibility to seizures, which can resume with the significant delay after termination of dietary treatment.