How to Diagnose SSADH

The diagnosis of SSADH is usually made after birth (postnatally) during infancy or childhood (or, in some cases, later in life), based upon a thorough clinical evaluation, identification of characteristic physical findings, and a variety of specialized tests.

Due to the nonspecific nature and variability of associated symptoms, experts suggest that SSADH should be considered in any individual with two or more features of intellectual, language, and motor delay and abnormally diminished muscle tone (hypotonia) of unknown cause (idiopathic).

Specialized testing to confirm a diagnosis of SSADH typically includes studies (i.e., quantitative organic acid analysis in an appropriate specialist laboratory) that may detect increased concentrations of 4-hydroxybutyric acid (4-HBA) in urine (i.e., 4-hydroxybutyric aciduria) and molecular genetic testing to confirm the abnormal gene from each parent in the patient.  (Note: As mentioned above, increased concentrations of 4-HBA may also be detected in plasma and cerebrospinal fluid. In addition, deficient SSADH activity has also been demonstrated in certain cells other than leukocytes.)

ALDH5A1 is the gene that codes for SSADH. Molecular genetic testing to identify bi-allelic mutations (abnormal changes found on both copies of a gene) or deletions in ALDH5A1 is used to make or confirm a diagnosis of SSADH. as noted above.  This testing is usually ordered by the patient’s pediatrician, primary care physician, neurologist or a genetic counselor and can be completed at a number of facilities around the world.  However, it is imperative that the testing facility specifically test for ALDH5A1.  Fortunately, diagnostic capabilities to identify SSADH via gene sequencing have been enhanced because a number of companies assess the sequence of this gene on panels of genes for idiopathic developmental delay, epilepsy, and other clinical features.