What are Neurotransmitter Diseases?
"Neurotransmitter Disease” is an umbrella term for genetic disorders that affect the synthesis, metabolism and catabolism of neurotransmitters. These inborn errors of metabolism affect the central nervous system and if left untreated can lead to severely compromised neurological function. The symptoms of some neurotransmitter diseases can be completely treated whereas in other neurotransmitter diseases treatment can sometimes improve quality of life.
Neurotransmitter Diseases are distinguishable by their respective affected neurotransmitters.
What is Succinic Semialdehyde Dehydrogenase Deficiency?
Succinic semialdehyde dehydrogenase deficiency (SSADH) is a rare
metabolic disorder characterized by lack of the enzyme involved in the
degradation of GABA, the major inhibitory neurotransmitter in the brain.
GABA controls the movements of humans, and when it is imbalanced,
major neurological abnormalities occur. In SSADH deficiency, neurotransmitters
are blocked from signaling one another correctly.
Due to the enzyme deficiency in SSADH patients, an unusual compound accumulates in the body, namely 4-hydroxybutyric acid (or gammahydroxybutyric acid; GHB). GHB is possibly a neurotransmitter like GABA, or at least at high concentrations it is likely a modulator of neurological activity in humans. GHB accumulation interferes with the patient’s, concentrate and process information in the brain.
What symptoms are associated with SSADH?
Symptoms associated with SSADH may be mild, moderate or severe and
often vary greatly from case to case. The symptoms of SSADH are caused
by the accumulation of GHB in the brain and include the following manifestations:
(*Defined as: common, > 70% of patients; frequent 30-70% of patients;
unusual, < 30% of patients)
• Delayed gross motor development
• Delayed mental development
• Delayed fine motor skill development
• Delayed speech and language development
• Behavioral problems
• Neonatal problems
• EEG abnormalities
• MRI or CT abnormalities
• Oculomotor apraxia
• Autistic features
What causes SSADH?
SSADH deficiency is inherited as an autosomal recessive trait. In recessive
disorders, the condition does not occur unless an individual inherits
the same defective gene for the same trait from each parent. A child
who receives one normal gene and one gene for the disease will be a
carrier but usually will not show symptoms. The risk of transmitting the
disease to the children of a couple, both of whom are carriers for a
recessive disorder, is 25 percent. 50 percent of their children risk being
carriers of the disease but generally will show no symptoms of the
disorder, 25 percent of their children may receive both normal genes,
one from each parent, and will be genetically normal for that trait. The
risk is the same for each pregnancy.
Who gets SSADH?
SSADH deficiency affects males and females in equal numbers. Approximately
350 cases of SSADH have been diagnosed throughout the world. However, it is believed that many SSADH patients are either undiagnosed or misdiagnosed.
How is SSADH diagnosed?
A diagnosis of SSADH deficiency is made based upon urine organic
profiling or blood amino acid analysis. For testing information contact K.
Michael Gibson Ph.D. or Phillip Pearl MD. Please contact Dr. Gibson by phone at
(906) 487-2025, fax at (906) 487-3167 or by email email@example.com.
Phillip L. Pearl, MD, Associate Professor of Pediatrics and Neurology at
The George Washington University School of Medicine and Pediatric
Neurologist at The Children’s National Medical Center in Washington, DC
maintains a SSADH database and is a clinical expert for SSADH deficiency
patients. Please contact Dr. Pearl by email at firstname.lastname@example.org or telephone at
How is SSADH treated?
Presently there is no known established and universally effective therapeutic
treatment for SSADH deficiency. In the longer term, medical
advancements made in gene therapy or stem cell transplantation may
provide an avenue to cure the disorder. In the shorter term, several
therapies have been tried or are currently being considered as listed
• Vigabitrin or Sabril - pharmacologically, the mode of action is an irreversible
inhibition of GABA-transaminase, leading to accumulation of
free and total GABA in the brain. The results of this therapy have
been encouraging in some patients, and of little to no value in others.
This medication has been suspended or avoided by some patients
due to the potential side effects.
• Lamotrigine - Pharmacologically, the mode of action is to inhibit the
release of excitatory amino acids, especially the major GABA precursor
glutamate, via inhibition of glutamic acid decarboxylase. Lamotrigine
has been successfully used and well tolerated in at lease one patient.
• NCS-382 antagonist - clinical trials on the use of this agent is pending.
In addition to the therapies listed above, several medications such as
prozac or Ritalin have been prescribed to assist in controlling behavioral
abnormalities. Extensive speech, physical and occupational therapy are
For a complete list of articles on SSADH, please refer to the Online
Mendelian Inheritance in Man (OMIM) which is linked below. Before
clicking, you will need to enter the following information at the OMIM site:
Key Words: “Succinic Semialdehyde Dehydrogenase Deficiency”
Access Listing: 271980
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