Gamma-Hydroxybutyrate (GHB) Content in Hair Samples Correlates Negatively with Age in Succinic Semialdehyde Dehydrogenase Deficiency

Abstract

Gamma-hydroxybutyrate (GHB) is a drug of abuse, an approved therapeutic for narcolepsy, an agent employed for facilitation of sexual assault, as well as a biomarker of succinic semialdehyde dehydrogenase deficiency (SSADHD). Our laboratory seeks to identify surrogate biomarkers in SSADHD that can shed light on the developmental course of this neurometabolic disease. Since GHB may be quantified in hair as a potential surrogate to identify victims of drug-related assault, we have opted to examine its level in SSADHD. We quantified GHB in hair derived from ten patients with SSADHD, and documented a significant negative age correlation. These findings are consistent with recent results in patient biological fluids, including plasma and red blood cells. These findings may provide additional insight into the developmental course of SSADHD (Jansen et al., J Inherit Metab Dis 39:795-800, 2016).

Keywords: GABA metabolism; Gamma-hydroxybutyrate (GHB); Hair analysis; Succinic semialdehyde dehydrogenase (SSADH); Succinic semialdehyde dehydrogenase deficiency (SSADHD); Tandem mass spectrometry.

Fig. 1

(Left) GHB concentrations in all hair segments measured from ten patients with SSADHD. Age and gender of patients are shown in the legend. (Right) Stratification of GHB content in hair segments in cm 1, 2, 3, and 4 for all patients from whom samples were available. Each data point for a patient hair sample represents a unique measurement of GHB content within that single 0.5–1.0 cm hair segment derived from the entire length of the hair sample (depicted as analysis from root to tip). Statistical analyses employed the Spearman rank order correlation, with significance set at the 95th centile

Fig. 2

Multiple reaction monitoring (MRM) of GHB in a representative hair sample from a patient with SSADHD and a control. The transition from m/z 103 > 85 was monitored with ²H₆-GHB as internal standard. This obviated interference from other potential contaminants, including other butyric acid compounds, which also elute at different retention times than GHB (Wang et al. 2016). The GHB level in the patient’s hair sample was approximately 5.9-fold increased in comparison to control based upon peak area

Fig. 3

Total hair GHB content for controls. The concentrations were calculated by standard addition method for each individual (age-dependent correlation was non-significant)