Molecular Characteristics
The ADK (Adenosine Kinase) gene is located at 10q22.2 and encodes a key enzyme in purine metabolism that phosphorylates adenosine to form AMP, regulating intracellular adenosine levels. ADK plays a critical role in maintaining adenosine homeostasis, which influences neurotransmission, methylation cycles, and hepatic function.
Mutations and Pathophysiology
Staufner et al. identified homozygous and compound heterozygous mutations in ADK (e.g., c.199C>T, p.Q67*; c.893C>A, p.A298D) in patients with ADK deficiency, a disorder characterized by developmental delay, seizures, and liver dysfunction.
Later, Alhusani A et al. reported a homozygous mutations in ADK. The affected individual had the phenotypical features described in the Professionals – Clinical characteristics section.
Loss of ADK function → impaired adenosine clearance → adenosine accumulation.
Purine metabolism disruption → ATP depletion.
Methylation defect (via SAH hydrolase inhibition) → global hypomethylation.
Neurological dysfunction: Adenosine excess alters GABA/glutamate balance, promoting seizures.
Hepatic toxicity: Adenosine-mediated mitochondrial dysfunction → steatosis/cholestasis.
Diagnostic Testing
Genetic testing: Whole-exome sequencing (WES) or targeted ADK gene panels.
Biochemical: Elevated plasma/urine adenosine (specialized metabolomics).
Supportive:
Brain MRI: Cerebral atrophy, white matter abnormalities.
Liver biopsy: Steatosis, cholestasis (if unexplained by other causes).
ADK