Rapid and sensitive detection of urinary 4-hydroxybutyric acid and its related compounds by gas chromatography–mass spectrometry in a patient with succinic semialdehyde dehydrogenase deficiency

We describe the rapid and sensitive detection of 4-hydroxybutyric acid, which is a marker compound for succinic semialdehyde dehydrogenase (SSADH) deficiency. Urinary 4-hydroxybutyric acid and 3,4-dihydroxybutyric acid were targeted, quantified by gas chromatography–mass spectrometry after simplified urease digestion in which lactone formation from γ-hydroxy acids is minimized. The recovery of 4-hydroxybutyric acid using this method was over 93%. 2,2-Dimethylsuccinic acid was used as an internal standard. The detection limit of this method was 1 nmol ml−1 for both 4-hydroxybutyric acid and 3,4-dihydroxybutyric acid. The urinary concentrations of 4-hydroxybutyric acid and of 3,4-dihydroxybutyric acid from the patient with an SSADH deficiency were 880–3628 mmol mol−1 creatinine (control; 3.3±3.3 mmol mol−1 creatinine) and 810–1366 mmol mol−1 creatinine (control; 67.4±56.2 mmol mol−1 creatinine), respectively. The simplified urease digestion of urine is very useful for quantifying 4-hydroxybutyric acid and its related compounds in patients with 4-hydroxybutyric aciduria.