Effect of genetically caused excess of brain gamma-hydroxybutyric acid and GABA on sleep

Sleep. 2005 Apr;28(4):418-24. doi: 10.1093/sleep/28.4.418.


Background: Exogenous gamma-hydroxybutyrate (GHB) increases slow-wave sleep and reduces daytime sleepiness and cataplexy in patients with primary narcolepsy.

Objective: To examine nighttime sleep and daytime sleepiness in a 13-year-old girl homozygous for succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare recessive metabolic disorder that disrupts the normal degradation of 4-aminobutyric acid (GABA), and leads to an accumulation of GHB and GABA within the brain.

Methods: Sleep interview, nighttime polysomnography, Multiple Sleep Latency Tests, and continuous 24-hour in-lab recordings in the patient; overnight polysomnography in her recessive mother and in a 13-year-old female control.

Results: During quiet wakefulness, background electroencephalographic activity was slow and composed of 7-Hz activity. Sleep stage 3/4 was slightly increased (28.1% of total sleep period, norms 15%-28%), and the daytime mean sleep latency was short in the patient (3 minutes 42 seconds, norms > 8 minutes). Stage 2 spindles were infrequent in the child (0.18/minute, norms: 1.2-9.2/minute) and her mother (0.65/minute) but normal (4.6/minute) in the control. At the beginning of the second night, a tonic-clonic seizure occurred, followed by a dramatic increase in stage 3/4 sleep, that lasted 46.3 % of the total sleep period, double the normal value. The mother showed a reduced total sleep time and rapid eye movement sleep percentage.

Discussion: This suggests that a chronic excess of GABA and GHB induces subtle sleep abnormalities, whereas increased slow-wave sleep evoked by a sudden event (here an epileptic seizure) may be caused by a supplementary increase in GABA and GHB.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Brain / metabolism*
  • Brain Diseases, Metabolic, Inborn / blood
  • Brain Diseases, Metabolic, Inborn / enzymology
  • Brain Diseases, Metabolic, Inborn / genetics
  • Disorders of Excessive Somnolence / diagnosis*
  • Disorders of Excessive Somnolence / physiopathology*
  • Electroencephalography
  • Female
  • Humans
  • Lymphocytes / enzymology
  • Methylmalonyl-CoA Decarboxylase / blood
  • Polysomnography
  • Sleep / physiology*
  • Sleep Stages / physiology
  • Sodium Oxybate / metabolism*
  • Sodium Oxybate / urine
  • Succinate-Semialdehyde Dehydrogenase / blood
  • Succinate-Semialdehyde Dehydrogenase / deficiency
  • Succinate-Semialdehyde Dehydrogenase / genetics*
  • Wakefulness / physiology
  • gamma-Aminobutyric Acid / genetics*
  • gamma-Aminobutyric Acid / metabolism*
  • gamma-Aminobutyric Acid / urine


  • gamma-Aminobutyric Acid
  • Sodium Oxybate
  • Succinate-Semialdehyde Dehydrogenase
  • Methylmalonyl-CoA Decarboxylase