4-Hydroxybutyrate is useful for diagnosing Succinic semialdehyde (SSADH) deficiency. This testing may also be used for assessment of Variants of Uncertain Significance (VUS) identified during genetic testing (e.g. Next Generation Sequencing or Capillary Sequencing Testing). Succinic semialdehyde dehydrogenase (SSADH) deficiency causes decreased succinic acid production from gamma-aminobutyric acid (GABA) with shunting of the accumulated succinic semialdehyde intermediate to 4-Hydroxybutyric acid and subsequently, 3,4-Hydroxybutyric acid. Gamma-aminobutyric acid functions as both a metabolic intermediate in neuronal and extra-neuronal tissues and as a neurotransmitter in neural tissue. Gamma-aminobutyric acid is found predominantly in brain cells; however, it also occurs in kidney and B-cells of the pancreas. Gamma-aminobutyric acid (GABA) is converted to succinic semialdehyde by GABA transaminase. Succinic semialdehyde is either metabolized to gamma hydrozybutryate (GHB) by GHB dehydrogenase or to succinate by SSADH. Deficiency of SSADH causes the accumulation of GHB in body fluids, which causes the clinical manifestations of SSADH deficiency, also known as 4-hydroxybutyric aciduria. Interestingly, despite the presence of increased serum concentrations of the organic acids, 4-Hydroxybutyric acid and 3,4-Hydroxybutyric acid SSADH deficiency is not associated with an increased anion gap or a metabolic acidosis because the molar concentrations of these acids in the blood are not sufficiently high enough to cause these abnormalities. The phenotype is that of diffuse encephalopathy, most often as a static condition, comprising psychomotor delays, ataxia, hypotonia, dysfunctional or absent speech, and variable seizures.
* Reference ranges may change over time. Please refer to the original patient report when evaluating results.
10 -14 days
Collect samples into 5 numbered 2.0 mL microcentrifuge tubes (or similar): Tube 1: 0.5 mL, Tube 2: 1.0 mL, Tube 3: 1.0 mL, Tube 4: 1.0 mL, Tube 5: 1.0 mL OR collect entire sample into a single sterile tube, which is considered a pooled CSF sample. Freeze.
Test sent to MNG Laboratories.