gamma-amino butyric acid metabolism disorder

Gamma-Amino Butyric Acid (GABA) Metabolism Disorder, also known as GABA-transaminase deficiency or succinic semialdehyde dehydrogenase (SSADH) deficiency, is a rare genetic disorder that affects the metabolism of the neurotransmitter GABA.

Characteristics:

• Inherited: The disorder is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Neonatal-infantile epileptic encephalopathy: Babies with this disorder are born with severe seizures and brain damage, which can lead to developmental delays and intellectual disability.
• Impairment of GABA catabolic pathway: The disorder is characterized by an impairment in the breakdown of GABA, leading to its accumulation in the body.

Types:

• GABA-transaminase deficiency: This is a specific type of GABA metabolism disorder caused by a deficiency of the enzyme GABA-transaminase.
• Succinic semialdehyde dehydrogenase (SSADH) deficiency: This is another type of GABA metabolism disorder caused by a deficiency of the enzyme SSADH.

Symptoms:

• Recurrent seizures: Babies with this disorder experience recurrent seizures, which can be severe and life-threatening.
• Developmental delays: Children with this disorder may experience developmental delays and intellectual disability due to brain damage.
• Epileptic encephalopathy: The disorder is characterized by a severe form of epilepsy that affects the brain.

References:

• [1] GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Babies with this disorder have recurrent seizures (epilepsy), ... [3]
• [2] Clinical disorders known to affect inherited gamma-amino butyric acid (GABA) metabolism are autosomal recessively inherited succinic semialdehyde dehydrogenase (SSADH) deficiency and homocarnosinosis. [1]
• [3] An amino acid metabolic disorder characterized by impairment of the GABA catabolic pathway. Traits & Categories for Gamma-Amino Butyric Acid Metabolism Disorder ... [5]
• [4] Apr 1, 2018 — GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Babies with this disorder have recurrent seizures ... [6]
• [5] Oct 14, 2024 — This term does not characterize a disease but a group of diseases. To learn about the diseases included under this term, you can consult the ... [7]
• [6] 3.3 Disorders of GABA metabolism. Amino butyric acid (GABA) metabolism is associated with several disorders, including GABA-transaminase deficiency, and ... [8]
• [7] gamma-amino butyric acid metabolism disorder. Definition, An amino acid metabolic disorder characterized by impairment of the GABA catabolic pathway. [9]

Common Signs and Symptoms

The signs and symptoms of gamma-amino butyric acid (GABA) metabolism disorders can vary in severity and presentation, but some common manifestations include:

• Recurrent Seizures: Babies with GABA-T deficiency have recurrent seizures (epilepsy), which can be a significant concern for parents and caregivers [1].
• Uncontrolled Limb Movements: Uncontrolled limb movements (choreoathetosis) are another symptom of this disorder, which can affect an individual's motor skills and coordination [5].
• Exaggerated Reflexes: Exaggerated reflexes (hyperreflexia) are also a common sign of GABA-T deficiency, indicating an abnormal response to stimuli [1][5].
• Weak Muscle Tone: Low muscle tone (hypotonia) is another symptom that can affect an individual's overall physical development and mobility [3].

Additional Symptoms

Other symptoms associated with GABA metabolism disorders include:

• Impaired Psychomotor Development: Individuals with this disorder may experience impaired psychomotor development, which can impact their cognitive and motor skills [2].
• Lethargy: Lethargy is another symptom that can be observed in individuals with GABA-T deficiency, indicating a lack of energy or motivation [2].
• High-Pitched Cry: A high-pitched cry is also a common sign of this disorder, which can be distressing for parents and caregivers [2].

References

[1] Apr 1, 2018 — Babies with this disorder have recurrent seizures (epilepsy), uncontrolled limb movements (choreoathetosis), exaggerated reflexes (hyperreflexia) ... [2] Manifestations reported include hypotonia, impaired psychomotor development, hyperreflexia, lethargy, seizures, high-pitched cry, accelerated linear growth and ... [3] The symptoms for an individual with GABA-T deficiency can include: psychomotor retardation (a slowing down of thought and activity), low muscle tone, ... [4] Apr 1, 2018 — Babies with this disorder have recurrent seizures (epilepsy), uncontrolled limb movements (choreoathetosis), exaggerated reflexes (hyperreflexia) ... [5] What are the signs and symptoms? · recurrent seizures (epilepsy) · uncontrolled limb movements (choreoathetosis) · exaggerated reflexes (hyperreflexia) · weak ...

Diagnostic Tests for Gamma-Amino Butyric Acid Metabolism Disorder

Gamma-amino butyric acid (GABA) metabolism disorder is a rare genetic disorder that affects the body's ability to metabolize GABA. Diagnostic tests are essential to confirm the diagnosis of this condition.

• Urine Organic Acid Testing: This test detects the presence of γ-hydroxybutyrate in the urine, which is a key indicator of GABA metabolism disorder [1].
• Magnetic Resonance Imaging (MRI): MRI scans can reveal consistent abnormalities in individuals with GABA-transaminase deficiency, a type of GABA metabolism disorder [1].
• Exome, Genome, and Sanger Sequencing: This integrated approach to diagnosis involves sequencing the genes responsible for GABA catabolism pathway abnormalities, including exome, genome, and Sanger sequencing [2][4].
• Clinical Findings: A thorough medical examination is necessary to identify symptoms such as hypotonia (low muscle tone) and other related clinical findings [8].
• Molecular Genetic Testing: This test confirms the diagnosis by showing mutations in the ABAT gene, which is responsible for GABA-transaminase activity [7].

It's essential to note that specialized testing of GHB in cerebrospinal fluid (CSF) may be required in some cases, and GABA levels should also be checked as part of the diagnostic process [6].

Treatment Options for GABA Metabolism Disorders

GABA (gamma-aminobutyric acid) metabolism disorders are a group of rare genetic conditions that affect the production or breakdown of GABA, leading to severe neurological and neuromuscular symptoms. While there is no cure for these disorders, various drug treatments can help manage the symptoms.

1. Vigabatrin: This anti-seizure medication has been shown to be effective in treating seizure disorders associated with GABA metabolism disorders [5]. It works by inhibiting the enzyme GABA transaminase, which is responsible for breaking down GABA.

2. Topiramate: Another anti-seizure medication, topiramate, has also been used to treat seizures and other symptoms of GABA metabolism disorders [5].

3. Rapamycin (Tor1 inhibitor): This drug has been investigated as a potential treatment for GABA metabolism disorders, particularly SSADH deficiency [10]. It works by inhibiting the mTOR pathway, which is involved in cellular growth and proliferation.

4. Other medications: In addition to these specific treatments, other medications such as benzodiazepines (e.g., Lyrica, gabapentin) may be prescribed to manage symptoms like anxiety, insomnia, or neuropathic pain [3].

It's essential to note that each individual with a GABA metabolism disorder may respond differently to these treatment options. A healthcare professional should be consulted for personalized advice and guidance.

References: [1] M Parviz (2014) - Cited by 81 [5] AD Kennedy (2019) - Cited by 31 [10] R Lakhani (2014) - Cited by 76

The differential diagnosis for disorders related to gamma-amino butyric acid (GABA) metabolism includes several conditions that can present with similar symptoms.

• GABA-transaminase deficiency: This is a rare genetic disorder characterized by the inability to break down GABA, leading to its accumulation in the body. It presents with severe neonatal-infantile epileptic encephalopathy and is often associated with recurrent seizures [1][4].
• Succinic semialdehyde dehydrogenase (SSADH) deficiency: This condition is also a genetic disorder that affects GABA metabolism, leading to the accumulation of GABA and its metabolite, gamma-hydroxybutyrate (GHB). It can present with similar symptoms to GABA-transaminase deficiency, including seizures and developmental delays [5].
• Homocarnosinosis: This is another rare genetic disorder that affects GABA metabolism, leading to the accumulation of homocarnosine in the body. It can present with similar symptoms to GABA-transaminase deficiency and SSADH deficiency, including seizures and developmental delays [2][8].

These conditions are often diagnosed through a combination of clinical evaluation, laboratory tests (such as urine amino acid analysis), and genetic testing.

References: [1] Context 1: Apr 1, 2018 — GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Babies with this disorder have recurrent seizures (epilepsy), ... [2] Context 2: by M Parviz · 2014 · Cited by 81 — The differential diagnosis for SSADH deficiency includes homocarnosinosis, but an enzyme defect ... [3] Context 3: by PL Pearl · 2006 · Cited by 31 — The known genetic disorders are GABA-transaminase deficiency, succinic semialdehyde dehydrogenase (SSADH) deficiency and homocarnosinosis. [4] Context 4: GABA-T deficiency is an extremely rare disorder of GABA metabolism characterized by a severe neonatal-infantile epileptic encephalopathy. [5] Context 5: by PL Pearl · 2015 · Cited by 53 — Diagnosis of SSADH deficiency is based on the accumulation of GABA and its metabolite, gamma-hydroxybutyrate (GHB), in the absence of SSADH.