Focal neurometabolic alterations in mice deficient for succinate semialdehyde dehydrogenase.

Metabolite profiling in succinate semialdehyde dehydrogenase (SSADH; Aldh5a1-/-) deficient mice previously revealed elevated gamma-hydroxybutyrate (GHB) and total GABA in urine and total brain and liver extracts. In this study, we extend our metabolic characterization of these mutant mice by documenting elevated GHB and total GABA in homogenates of mutant kidney, pancreas and heart. We quantified beta-alanine (a GABA homolog and putative neurotransmitter) to address its potential role in pathophysiology.

Plasma creatinine assessment in creatine deficiency: A diagnostic pitfall.

Guanidinoacetate methyltransferase (GAMT) deficiency (creatine deficiency syndrome) is a recently discovered inborn error of creatine biosynthesis. Affected patients have elevated concentrations of guanidino-acetate, the metabolic precursor of creatine, in urine, plasma and cerebrospinal fluid. In addition, urinary creatinine excretion and plasma creatinine concentration are decreased.

Quantitative analysis of urinary acylglycines for the diagnosis of beta-oxidation defects using GC-NCI-MS.

The analysis of acylglycines is an important biochemical tool for the diagnosis of inherited disorders of mitochondrial fatty acid beta-oxidation. A stable isotope dilution gas chromatography negative chemical ionisation mass spectrometry method for the quantitative analysis of short- and medium-chain acylglycines as their bis(trifluoromethyl)benzyl (BTFMB) ester derivatives is described. The diagnostic usefulness of the method was demonstrated in nine patients with medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) deficiency, and seven patients with multiple acyl-CoA dehydrogenation defect (MAD).

Combined method for the determination of gamma-aminobutyric and beta-alanine in cerebrospinal fluid by stable isotope dilution mass spectrometry.

A previously described method for the determination of GABA in CSF has been expanded to include both GABA and beta-ALA, using a single GC-MS analysis. A stable isotope labelled internal standard for beta-ALA was synthesised to achieve accurate quantification. This new combined method expands the diagnostic power compared to an isolated GABA measurement.