N-acetyl glutamate synthetase deficiency

=N-Acetyl Glutamate Synthetase Deficiency = N-Acetyl Glutamate Synthetase Deficiency (NAGS deficiency) is a rare genetic disorder that affects the urea cycle, a series of biochemical reactions that occur in the liver. This cycle is crucial for removing ammonia, a toxic byproduct of protein metabolism, from the bloodstream.

Overview

NAGS deficiency is characterized by a deficiency of the enzyme N-acetyl glutamate synthetase, which is essential for the activation of carbamoyl phosphate synthetase I, the first enzyme in the urea cycle. Without this activation, the urea cycle cannot proceed, leading to the accumulation of ammonia in the blood, a condition known as hyperammonemia.

Symptoms

The symptoms of NAGS deficiency can vary widely but often include:

• Lethargy
• Vomiting
• Poor feeding
• Hypotonia (reduced muscle tone)
• Seizures
• Coma

In severe cases, the condition can be life-threatening if not treated promptly.

Diagnosis

Diagnosis of NAGS deficiency typically involves:

• Genetic testing to identify mutations in the NAGS gene.
• Measurement of ammonia levels in the blood.
• Analysis of amino acid levels in the plasma.

Treatment

Treatment for NAGS deficiency focuses on reducing ammonia levels and may include:

• Dietary management to limit protein intake.
• Medications such as carglumic acid, which can activate carbamoyl phosphate synthetase I in the absence of N-acetyl glutamate.
• In severe cases, dialysis may be necessary to remove excess ammonia from the blood.

Genetics

NAGS deficiency is inherited in an autosomal recessive pattern, meaning that both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Prognosis

The prognosis for individuals with NAGS deficiency varies depending on the severity of the condition and the timeliness of treatment. Early diagnosis and management are crucial for preventing serious complications and improving outcomes.

Research

Ongoing research is focused on better understanding the genetic and biochemical mechanisms of NAGS deficiency, as well as developing more effective treatments.

See Also

• Urea cycle disorders
• Hyperammonemia
• Metabolic disorders

External Links

• N-Acetylglutamate Synthetase Deficiency - Genetic and Rare Diseases Information Center
• Orphanet: N-Acetylglutamate Synthetase Deficiency

NIH genetic and rare disease info

• NIH info on N-acetyl glutamate synthetase deficiency

N-acetyl glutamate synthetase deficiency is a rare disease.