SSADH deficiency possibly associated with enzyme activity-reducing SNPs

Tomoyuki Akiyama, Hitoshi Osaka, Hiroko Shimbo, Tomiko Kuhara, Takashi Shibata, Katsuhiro Kobayashi, Kenji Kurosawa, Harumi Yoshinaga

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Background Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder that affects the degradation of gamma-aminobutyric acid and leads to the accumulation of gamma-hydroxybutyric acid (GHB) in body fluids. Diagnosis of SSADH deficiency is challenging, since the neurological symptoms are non-specific. Case The patient is a nine-year-old Japanese boy who presented with developmental delay, autism, epilepsy, and episodic gait disturbance. Brain magnetic resonance imaging showed hyperintense lesions in the bilateral thalami, globus pallidi, substantia nigra, and dentate nuclei. Urine metabolome analysis revealed elevated GHB, which led to a biochemical diagnosis of SSADH deficiency. Genetic analysis of the ALDH5A1 gene revealed a novel missense mutation c.1586G>A inherited from his father. It also demonstrated three single nucleotide polymorphisms (SNPs) (c.106G>C, c.538C>T, and c.545C>T), all of which were inherited from his mother and are known to reduce SSADH enzyme activity. There were no duplications or deletions in other exons in the patient or his parents. No variants in the upstream, intronic, or downstream regions of the ALDH5A1 gene were found in the patient. Enzymatic assay revealed a marked reduction of SSADH enzyme activity (≈2% of the lower limit of the normal range). Conclusion Although other mechanisms cannot be fully excluded, the clinical manifestation of SSADH deficiency in this patient may be attributed to the combined effect of the mutation and the three enzyme activity-reducing SNPs. Urine metabolome analysis effectively detected his elevated GHB and is thus considered to be a good screening method for this underdiagnosed and potentially manageable metabolic disorder.

Original languageEnglish
Pages (from-to)871-874
Number of pages4
JournalBrain and Development
Issue number9
Publication statusPublished - 2016


  • ALDH5A1 gene
  • Gamma-aminobutyric acid
  • Gamma-hydroxybutyric acid
  • Metabolome analysis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology


Dive into the research topics of 'SSADH deficiency possibly associated with enzyme activity-reducing SNPs'. Together they form a unique fingerprint.

Cite this