ASL deficiency

ASL Deficiency Adenylosuccinate lyase (ASL) deficiency is a rare genetic disorder that affects the body's ability to break down certain molecules involved in the production of energy and the synthesis of nucleotides. This condition is characterized by a range of symptoms that can vary in severity and may include developmental delay, neurological issues, and metabolic abnormalities.

Overview

ASL deficiency is an autosomal recessive disorder caused by mutations in the ASL gene, which provides instructions for making the enzyme adenylosuccinate lyase. This enzyme plays a crucial role in two metabolic pathways: the purine nucleotide cycle and the de novo synthesis of purine nucleotides.

Symptoms

The symptoms of ASL deficiency can vary widely among affected individuals. Common symptoms include:

• Developmental delay
• Intellectual disability
• Seizures
• Autistic features
• Muscle weakness
• Feeding difficulties

Pathophysiology

The ASL enzyme is involved in the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate to adenosine monophosphate (AMP). Deficiency in ASL activity leads to the accumulation of SAICAR and succinyladenosine, which are toxic to the brain and other tissues.

Diagnosis

Diagnosis of ASL deficiency is typically based on clinical symptoms, biochemical testing, and genetic testing. Elevated levels of succinyladenosine in urine or cerebrospinal fluid are indicative of the disorder. Genetic testing can confirm mutations in the ASL gene.

Treatment

Currently, there is no cure for ASL deficiency. Treatment is supportive and focuses on managing symptoms. This may include:

• Antiepileptic drugs for seizures
• Physical therapy
• Nutritional support

Prognosis

The prognosis for individuals with ASL deficiency varies depending on the severity of the condition. Some individuals may have a mild form with minimal symptoms, while others may experience significant neurological impairment.

Research

Ongoing research is focused on understanding the molecular mechanisms of ASL deficiency and developing potential therapies. Gene therapy and enzyme replacement therapy are areas of active investigation.

See Also

• Purine metabolism disorders
• Inborn errors of metabolism

External Links

• Genetic and Rare Diseases Information Center (GARD)
• National Organization for Rare Disorders (NORD)

NIH genetic and rare disease info

• NIH info on ASL deficiency

ASL deficiency is a rare disease.