SSADH (succinic semialdehyde dehydrogenase deficiency)

Succinic semialdehyde dehydrogenase deficiency
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Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Developmental delay, hypotonia, ataxia, seizures, autism spectrum disorder
Complications	N/A
Onset	Infancy or early childhood
Duration	Lifelong
Types	N/A
Causes	Genetic mutation in the ALDH5A1 gene
Risks	N/A
Diagnosis	Genetic testing, MRI, EEG
Differential diagnosis	N/A
Prevention	N/A
Treatment	Symptomatic treatment, dietary management
Medication	N/A
Prognosis	Variable
Frequency	Rare
Deaths	N/A

Succinic semialdehyde dehydrogenase deficiency (SSADH deficiency) is a rare autosomal recessive metabolic disorder that affects the breakdown of the neurotransmitter gamma-aminobutyric acid (GABA). It is caused by mutations in the ALDH5A1 gene, which encodes the enzyme succinic semialdehyde dehydrogenase. This enzyme is crucial for the degradation of GABA, and its deficiency leads to the accumulation of GABA and gamma-hydroxybutyric acid (GHB) in the body.

Pathophysiology

SSADH deficiency results from a defect in the GABA shunt, a metabolic pathway that converts GABA into succinic acid, which then enters the Krebs cycle. The deficiency of the enzyme succinic semialdehyde dehydrogenase leads to the accumulation of succinic semialdehyde, which is then converted into GHB. Elevated levels of GABA and GHB can affect the central nervous system, leading to the neurological symptoms observed in affected individuals.

Clinical Features

The clinical presentation of SSADH deficiency is highly variable, but common features include:

• Developmental delay and intellectual disability
• Hypotonia (decreased muscle tone)
• Ataxia (lack of voluntary coordination of muscle movements)
• Seizures
• Behavioral problems, including features of autism spectrum disorder
• Sleep disturbances

Diagnosis

Diagnosis of SSADH deficiency is based on clinical evaluation, biochemical testing, and genetic testing. Elevated levels of GHB in the urine are indicative of the disorder. Magnetic resonance imaging (MRI) of the brain may show characteristic findings, and electroencephalogram (EEG) may reveal abnormalities consistent with seizure activity. Definitive diagnosis is achieved through genetic testing to identify mutations in the ALDH5A1 gene.

Management

There is currently no cure for SSADH deficiency, and treatment is primarily symptomatic. Management strategies include:

• Antiepileptic drugs to control seizures
• Physical and occupational therapy to address motor and developmental delays
• Behavioral therapy and educational interventions for autism spectrum disorder features
• Dietary modifications, such as a ketogenic diet, may be beneficial in some cases

Prognosis

The prognosis for individuals with SSADH deficiency varies widely. Some individuals may have mild symptoms and lead relatively normal lives, while others may experience significant neurological impairment. Early diagnosis and intervention can improve outcomes.

Also see

• Gamma-aminobutyric acid
• Metabolic disorder
• Autosomal recessive disorder
• Genetic testing

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External links

• Comprehensive information from the National Institute of health.
  

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