ABSTRACT

4-Hydroxybutyric acid was once developed as an intravenous anesthetic in order to obtain an analog of glutamate and 4-aminobutyrate, which would cross the blood–brain barrier. Impaired psychomotor development, hypotonia, ataxia, behavioral dysregulation, hyporeflexia, and epilepsy are the main features of patients with 4-hydroxybutyric aciduria and may be severe. The molecular defect in 4-hydroxybutyric aciduria is in the enzyme succinic semialdehyde hydrogenase. The immediate consequence of the metabolic block is the accumulation of 4-hydroxybutyric acid. 4-Hydroxybutyric acid is not readily detected in the cerebrospinal fluid of control individuals. Quantification of this compound, even in patients, may be spuriously low. A stable isotope dilution, internal standard method has revealed consistently higher levels and would also be best for prenatal diagnosis. The immediate consequence of the metabolic block is the accumulation of 4-hydroxybutyric acid. This compound has been found in large amounts in the urine in all of the studied patients.