[Succinic semialdehyde dehydrogenase deficiency].

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Succinic semialdehyde dehydrogenase (SSADH) deficiency is an ultra-rare autosomal recessive metabolic disorder.
• It results from mutations in the ALDH5A1 gene, affecting GABA metabolism.
• This deficiency leads to the accumulation of neurotoxic metabolites.

Observation:

• Three infant cases of SSADH deficiency are presented.
• Clinical symptoms included developmental delay, intellectual disability, hypotonia, hyporeflexia, and seizures.
• Electroencephalogram (EEG) revealed background slowing and focal spikes; Head MRI showed basal ganglia damage and cerebral peduncle abnormalities in two patients.

Findings:

• Urinary organic acid analysis using gas chromatography-mass spectrometry (GC-MS) identified elevated levels of 4-hydroxybutyrate (GHB) in all three patients.
• Diagnosis was confirmed by correlating clinical symptoms with biochemical findings.
• This highlights the diagnostic utility of urinary organic acid profiling.

Implications:

• Early identification of SSADH deficiency is critical for timely intervention.
• Urine organic acid analysis is essential for diagnosing children with unexplained intellectual disability, epilepsy, or neuropsychiatric disturbances.
• Prompt diagnosis can guide management and potentially improve neurodevelopmental outcomes.