PET Imaging of GABA Receptors in Succinic Semialdehyde Dehydrogenase Deficiency
Condition: Succinic Semialdehyde Dehydrogenase Deficiency; SSADH Deficiency
MeSH terms: Amino Acid Metabolism, Inborn Errors; Developmental Disabilities
Study type: Observational

Summary: 
      This study will use brain imaging to map brain cell receptors for a chemical called GABA, a
      chemical that inhibits the activities of nerve cells. The study includes patients with
      succinic semialdehyde dehydrogenase deficiency, or SSADH (a disorder in which an enzyme
      deficiency disrupts GABA metabolism), their parents, and healthy volunteers. SSADH deficiency
      causes various neurological and neuromuscular problems, including mild to severe mental
      retardation, delays in the acquisition of skills requiring the coordination of mental and
      physical activities (psychomotor retardation), delays in language and speech development, and
      other symptoms.

      Healthy volunteers 18-55 years of age, patients with SSADH between 5 and 24 years of age, and
      parents of patients 18-55 years of age may be eligible for this study.

      Participants undergo magnetic resonance imaging (MRI) and positron emission tomography (PET)
      scanning as follows:

      Magnetic resonance imaging

      MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For
      this procedure, the subject lies on a table that is moved into the scanner (a narrow metal
      cylinder surrounded by a magnetic field) wearing earplugs to muffle loud knocking and
      thumping sounds that occur during the scanning process. Scanning time varies from 20 minutes
      to 3 hours, with most scans lasting between 45 and 90 minutes. Participants may be asked to
      lie still for up to 90 minutes at a time. In addition to standard MRI, participants may also
      have new types of MRI that may detect brain abnormalities when regular MRI is normal, such as
      diffusion tensor MRI and magnetic resonance spectroscopy. There are no noticeable differences
      from ordinary MRI scans.

      Positron Emission Tomography

      A catheter (plastic tube) is placed in a vein in the subject's wrist. The subject lies on a
      table with his or her head placed in the scanner. A mask, used to help keep the head still in
      the scanner, is placed over the head. The mask is not uncomfortable and has holes for the
      subject to see through. A radioactive compound called flumazenil is injected into a vein. The
      scan takes about 90 minutes.

      Some children need to be sedated for PET or MRI scans. In these cases, chloral hydrate, a
      standard drug for pediatric diagnostic procedures, is used.

      ...
    

Detailed description: 
      Objective: To measure CNS GABA receptors and GABA levels in patients with succinic
      semialdehyde dehydrogenase (SSADH) deficiency, a severe pediatric neurotransmitter disease.

      Study Population: The study will include children and young adult patients with the disorder,
      as well as parents of patients (obligate heterozygotes), and adult normal volunteers.

      Design: this is a natural history study using neuroimaging techniques. We will perform
      11C-flumazenil PET scans, and magnetic resonance spectroscopy (MRS). We will perform
      neurological examinations to obtain data on clinical manifestations of the condition.

      Outcome measures: The outcome measures will be the distribution of CNS binding of
      11C-flumazenil, and brain GABA levels measured by MRS, and their relation to clinical
      manifestations such as motor, speech, and language impairment, hypotonia, hyporreflexia, and
      seizures. We expect to show that patients with SSADH deficiency will have multifocal
      reductions in FMZ binding and increased brain GABA levels in a similar pattern.
    

Keywords: Seizures; Development; Pediatric; Benzodiazepine Receptors; Neurotransmission; Succinic Semialdehyde Dehydrogenase; Deficiency; SSADH Deficiency; Healthy Volunteer; HV