Alpha-aminoadipic and alpha-ketoadipic aciduria

Autosomal recessive - en

Alpha-aminoadipic and alpha-ketoadipic aciduria is a rare metabolic disorder characterized by the abnormal accumulation and excretion of alpha-aminoadipic acid and alpha-ketoadipic acid in the urine. This condition is part of a group of disorders known as amino acidurias, which involve the improper processing of amino acids due to deficiencies in certain enzymes or transporters. Alpha-aminoadipic and alpha-ketoadipic aciduria is specifically related to disruptions in the lysine degradation pathway, which is essential for the breakdown and utilization of the amino acid lysine.

Causes

The disorder is caused by genetic mutations that affect the enzymes responsible for the catabolism of lysine, particularly in the steps involving the conversion of lysine to alpha-aminoadipic acid and subsequently to alpha-ketoadipic acid. These enzymes include aminoadipic semialdehyde synthase, which is crucial for the conversion process. Genetic mutations that impair the function of these enzymes can lead to the accumulation of their substrates, resulting in alpha-aminoadipic and alpha-ketoadipic aciduria.

Symptoms

The clinical presentation of individuals with alpha-aminoadipic and alpha-ketoadipic aciduria can vary widely. Some individuals may be asymptomatic and diagnosed incidentally through urine tests, while others may present with neurological symptoms such as developmental delay, intellectual disability, seizures, and muscle hypotonia. The variability in symptoms is likely due to differences in the extent of enzyme deficiency and the accumulation of toxic metabolites.

Diagnosis

Diagnosis of alpha-aminoadipic and alpha-ketoadipic aciduria is typically made through the detection of elevated levels of alpha-aminoadipic acid and alpha-ketoadipic acid in the urine using techniques such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS). Genetic testing may also be performed to identify mutations in the genes responsible for the enzyme deficiencies.

Treatment

There is no specific treatment for alpha-aminoadipic and alpha-ketoadipic aciduria. Management of the condition is supportive and may include dietary modifications to restrict lysine intake, although the effectiveness of this approach is uncertain. Treatment of symptoms such as seizures is managed according to standard protocols for those conditions.

Prognosis

The long-term outlook for individuals with alpha-aminoadipic and alpha-ketoadipic aciduria varies depending on the severity of the enzyme deficiency and the presence of neurological symptoms. Early detection and management of symptoms can improve the quality of life for affected individuals.