Adenylosuccinate lyase deficiency (ADSL deficiency, ADSLD) is an ultra-rare inherited disorder of purine metabolism caused byreduced activity of the adenylosuccinate lyase (ADSL) enzyme.
The condition primarily affects the nervous system, but its severity varies considerably between patients. Common features may include developmental delay, intellectual disability, low muscle tone (hypotonia), seizures,autistic features and difficulties with movement or communication.The clinical spectrum ranges from relatively mild presentations to severe forms appearing during infancy or, rarely, in the neonatal period.
ADSL deficiency is inherited in an autosomal recessive manner. This means that the patient has inherited a disease-causing variant of the ADSL gene from each parent. Parents are usually healthy carriers.
Today, ADSL deficiency is frequently first identified by genetic testing, particularly whole-exome sequencing (WES), which reveals pathogenic or likely pathogenic variants in the ADSL gene.
The genetic finding can then be supported by biochemical testing. Patients with ADSL deficiency typically accumulate the characteristic metabolites SAdo and SAICAr, which can be measured in biological samples, particularly urine.
There is currently no approved disease-modifying treatment for ADSL deficiency. Medical care is therefore focused on individual symptoms and may include treatment of seizures, as well as developmental, neurological and rehabilitation support.
At the same time, research into ADSL deficiency is progressing. Our group studies the molecular mechanisms of the disease and develops experimental therapeutic approaches, including gene therapy. These approaches are currently at the research and preclinical stage.
Families affected by ADSL deficiency can connect with the Rare Birds Foundation for ADSLD, an international patient organization supporting individuals and families affected by ADSL deficiency.
The Foundation connects families, shares information about ongoing research and provides resources for newly diagnosed patients and their families. Nicole Lytle is one of the key patient advocates behind the organization and works closely with families, researchers and clinicians.
You can also follow the ADSL deficiency community on Instagram:@ADSLdeficiency.
Illustration created using Canva.
